Trial Outcomes & Findings for A Study of Chemo +/- Low-dose Radiation as Induction Therapy in SCCHN (NCT NCT02126969)

Last Updated: 2023-03-13

Results Overview

Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Up to 50 days

Results posted on

2023-03-13

Participant Flow

Participant milestones

Participant milestones
Measure	Chemotherapy Plus Radiation Therapy Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Overall Study STARTED	23	22
Overall Study COMPLETED	22	20
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemotherapy Plus Radiation Therapy Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

A Study of Chemo +/- Low-dose Radiation as Induction Therapy in SCCHN

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy Plus Radiation Therapy n=23 Participants Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=22 Participants Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation	Total n=45 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 6.7 • n=99 Participants	55 years STANDARD_DEVIATION 8.1 • n=107 Participants	57 years STANDARD_DEVIATION 7.4 • n=206 Participants
Sex: Female, Male Female	5 Participants n=99 Participants	2 Participants n=107 Participants	7 Participants n=206 Participants
Sex: Female, Male Male	18 Participants n=99 Participants	20 Participants n=107 Participants	38 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=99 Participants	21 Participants n=107 Participants	44 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	22 Participants n=99 Participants	22 Participants n=107 Participants	44 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	23 participants n=99 Participants	22 participants n=107 Participants	45 participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 50 days

Outcome measures

Outcome measures
Measure	Chemotherapy Plus Radiation Therapy n=22 Participants Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=20 Participants Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Primary Site Complete Response Rate	6 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 50 days

To assess overall response rate of patients to 2 cycles of induction Docetaxel and Carboplatin with or without LDFRT. Response assessment was Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and Progressive Disease (PD): \> 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Chemotherapy Plus Radiation Therapy n=22 Participants Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=20 Participants Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Overall Response Rate Overall Complete Response Rate	1 Participants	1 Participants
Overall Response Rate Overall Partial Response Rate	11 Participants	12 Participants
Overall Response Rate Overall Stable Disease Rate	10 Participants	7 Participants
Overall Response Rate overall Progressive Disease Rate	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 50 days (pre- and post-treatment)

Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey. 1. Physical; scores range from 7-35; higher scores indicate increased well-being 2. Social/family; scores range from 7-35; higher scores indicate increased well-being 3. Emotional; scores range from 6-30; higher scores indicate increased well-being 4. Functional; scores range from 7-35; higher scores indicate increased well-being 5. Additional Concerns; scores range from 10-50; lower scores indicate increased well-being 6. FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being 7. FACT-H\&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being 8. Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being

Outcome measures

Outcome measures
Measure	Chemotherapy Plus Radiation Therapy n=22 Participants Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=20 Participants Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. PHYSICAL WELL-BEING SCORE	-1.46 change in score Standard Deviation 5.12	-1.64 change in score Standard Deviation 7.22
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. SOCIAL/FAMILY WELL-BEING SCORE	-1.34 change in score Standard Deviation 4.55	-2.34 change in score Standard Deviation 3.72
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. EMOTIONAL WELL-BEING SCORE	2.05 change in score Standard Deviation 3.75	1.60 change in score Standard Deviation 4.31
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. FUNCTIONAL WELL-BEING SCORE	-0.48 change in score Standard Deviation 6.04	-1.70 change in score Standard Deviation 4.92
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. FACT-G TOTAL SCORE	-1.23 change in score Standard Deviation 13.52	-4.08 change in score Standard Deviation 12.72
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. ADDITIONAL CONCERNS SCORE	5.01 change in score Standard Deviation 8.24	3.63 change in score Standard Deviation 7.80
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. FACT-H&N TOTAL SCORE	3.79 change in score Standard Deviation 18.05	-0.46 change in score Standard Deviation 19.16
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. TRIAL OUTCOME INDEX SCORE	3.08 change in score Standard Deviation 14.55	0.29 change in score Standard Deviation 15.05

SECONDARY outcome

Timeframe: From date of randomization until date of death from any cause, assessed up to 3 years

3-year overall survival

Outcome measures

Outcome measures
Measure	Chemotherapy Plus Radiation Therapy n=22 Participants Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=20 Participants Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
3-year Overall Survival	14 Participants	11 Participants

Adverse Events

Chemotherapy Plus Radiation Therapy

Serious events: 12 serious events

Other events: 22 other events

Deaths: 8 deaths

Chemotherapy Without Radiation

Serious events: 6 serious events

Other events: 20 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Susanne Arnold

University of Kentucky

Phone: 8592579568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Chemotherapy Plus Radiation Therapy n=22 participants at risk Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=20 participants at risk Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Blood and lymphatic system disorders Febrile neutropenia	22.7% 5/22 • Number of events 5 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Cardiac disorders Cardiac arrest	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Abdominal pain	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Dysphagia	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Esophagitis	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Nausea	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Vomiting	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Infections and infestations - Other, specify	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Sepsis	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Skin infection	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Lung infection	22.7% 5/22 • Number of events 6 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Investigations Neutrophil count decreased	13.6% 3/22 • Number of events 3 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Investigations White blood cell decreased	18.2% 4/22 • Number of events 4 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Metabolism and nutrition disorders Hyperglycemia	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Metabolism and nutrition disorders Hypoglycemia	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Metabolism and nutrition disorders Glucose intolerance	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Nervous system disorders Syncope	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Respiratory, thoracic and mediastinal disorders Laryngeal edema	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Respiratory, thoracic and mediastinal disorders Laryngeal obstruction	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Vascular disorders Hypotension	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.

Other adverse events
Measure	Chemotherapy Plus Radiation Therapy n=22 participants at risk Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy Without Radiation n=20 participants at risk Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Blood and lymphatic system disorders Anemia	13.6% 3/22 • Number of events 5 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	35.0% 7/20 • Number of events 9 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Blood and lymphatic system disorders Febrile neutropenia	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Cardiac disorders Sinus tachycardia	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Cardiac disorders Left ventricular systolic dysfunction	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Ear and labyrinth disorders Hearing impaired	22.7% 5/22 • Number of events 6 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	10.0% 2/20 • Number of events 3 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Ear and labyrinth disorders Tinnitus	22.7% 5/22 • Number of events 6 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	30.0% 6/20 • Number of events 6 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Eye disorders Blurred vision	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Abdominal pain	13.6% 3/22 • Number of events 4 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	15.0% 3/20 • Number of events 3 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Constipation	50.0% 11/22 • Number of events 11 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	45.0% 9/20 • Number of events 9 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Diarrhea	36.4% 8/22 • Number of events 8 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	20.0% 4/20 • Number of events 7 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Dry mouth	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	25.0% 5/20 • Number of events 5 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Dyspepsia	13.6% 3/22 • Number of events 3 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Dysphagia	18.2% 4/22 • Number of events 5 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	25.0% 5/20 • Number of events 6 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Esophagitis	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Mucositis oral	81.8% 18/22 • Number of events 53 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	90.0% 18/20 • Number of events 41 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Nausea	72.7% 16/22 • Number of events 24 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	80.0% 16/20 • Number of events 24 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Rectal hemorrhage	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Vomiting	63.6% 14/22 • Number of events 19 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	45.0% 9/20 • Number of events 11 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Oral cavity fistula	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Gastrointestinal disorders Gastroesophageal reflux disease	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Fatigue	36.4% 8/22 • Number of events 10 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	45.0% 9/20 • Number of events 11 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Fever	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	10.0% 2/20 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Injection site reaction	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Pain	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Edema limbs	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Infusion related reaction	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
General disorders Non-cardiac chest pain	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Hepatobiliary disorders Hepatic failure	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Immune system disorders Allergic reaction	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Conjunctivitis infective	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Otitis media	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Salivary gland infection	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Sepsis	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Sinusitis	4.5% 1/22 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	0.00% 0/20 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Skin infection	9.1% 2/22 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Tracheitis	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Upper respiratory infection	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	10.0% 2/20 • Number of events 2 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Urinary tract infection	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Vaginal infection	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.
Infections and infestations Wound infection	0.00% 0/22 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.	5.0% 1/20 • Number of events 1 • The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject, mortality assessed up to 3 years.