Trial Outcomes & Findings for Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer (NCT NCT02031250)

NCT ID: NCT02031250

Last Updated: 2026-03-02

Results Overview

Kaplan-Meier curves with point-wise 90% confidence intervals will be generated for each treatment arm, overall and by strata. Estimates with confidence intervals will be generated from these curves for the usual summary statistics, including median DFS times.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

106 participants

Primary outcome timeframe

2 years post start of treatment

Results posted on

2026-03-02

Participant Flow

132 patients were screened resulting in 26 screen failures. 6 patients were enrolled but withdrew from the study before being randomized

Participant milestones

Participant milestones
Measure	Control Arm Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Overall Study STARTED	59	41
Overall Study COMPLETED	54	40
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Control Arm Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Overall Study Noncompliance	1	1
Overall Study Withdrawal by Subject	4	0

Baseline Characteristics

Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control Arm n=59 Participants Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=41 Participants Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes	Total n=100 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=41 Participants	26 Participants n=35 Participants	60 Participants n=76 Participants
Age, Categorical >=65 years	25 Participants n=41 Participants	15 Participants n=35 Participants	40 Participants n=76 Participants
Sex: Female, Male Female	5 Participants n=41 Participants	6 Participants n=35 Participants	11 Participants n=76 Participants
Sex: Female, Male Male	54 Participants n=41 Participants	35 Participants n=35 Participants	89 Participants n=76 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=41 Participants	36 Participants n=35 Participants	85 Participants n=76 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=41 Participants	5 Participants n=35 Participants	15 Participants n=76 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=41 Participants	1 Participants n=35 Participants	2 Participants n=76 Participants
Race (NIH/OMB) Asian	1 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=76 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants
Race (NIH/OMB) Black or African American	1 Participants n=41 Participants	1 Participants n=35 Participants	2 Participants n=76 Participants
Race (NIH/OMB) White	45 Participants n=41 Participants	34 Participants n=35 Participants	79 Participants n=76 Participants
Race (NIH/OMB) More than one race	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=41 Participants	5 Participants n=35 Participants	16 Participants n=76 Participants
Region of Enrollment United States	59 participants n=41 Participants	41 participants n=35 Participants	100 participants n=76 Participants

PRIMARY outcome

Timeframe: 2 years post start of treatment

Outcome measures

Outcome measures
Measure	Control Arm n=41 Participants Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=40 Participants Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Disease Free Survival (DSF) Time- 2 Year Estimate	48 days Interval 34.0 to 60.0	57 days Interval 43.0 to 69.0

SECONDARY outcome

Timeframe: 2 years post-treatment

Compare local-regional control rates between the two arms at 1, 2 and 3 years. Local-regional control is defined as the absence of local-regional progression. Locoregional failure (LRF) time was defined as the time from date of diagnosis to local or regional progression. Patients without LRF at last follow-up were censored at date of last follow-up.

Outcome measures

Outcome measures
Measure	Control Arm n=41 Participants Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=40 Participants Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Local-regional Control Rate	15 participants	7 participants

SECONDARY outcome

Timeframe: 3 years post treatment

Outcome measures

Outcome measures
Measure	Control Arm n=41 Participants Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=40 Participants Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Proportion of Patients in Which Hypoperfused/Low-diffusion Subvolumes Overlap With Recurrence Volumes	12 Participants	12 Participants

SECONDARY outcome

Timeframe: 3 years post treatment

Acute and late toxicities will be summarized descriptively by grade and type for each treatment group. The Percent of patients experiencing certain toxicity types will be calculated with score based confidence intervals. Chi-square tests will be used to test whether the proportion of patients with toxicity differs between treatment groups. ACUTE TOXICITIES ≤3MONTHS AFTER RT. LATE TOXICITIES \>3MONTHS AFTER RT

Outcome measures

Outcome measures
Measure	Control Arm n=41 Participants Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=40 Participants Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Percent of Patients With Adverse Events ACUTE TOXICITIES - Hospitalization	21.9 Percent of patients	25.6 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- Interrupted chemotherapy	24.4 Percent of patients	23.1 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- feeding tube	24.4 Percent of patients	38.5 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- Pain requiring long active narcotics	43.9 Percent of patients	52.6 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- RT delay	2.5 Percent of patients	0 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- Dehydration requiring IVF Support	53.7 Percent of patients	46.2 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- Grade 2+ mucositis	80 Percent of patients	73 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- Grade 3+ mucositis	9.8 Percent of patients	10.0 Percent of patients
Percent of Patients With Adverse Events ACUTE TOXICITIES- Grade 3+ dermatitis	2.4 Percent of patients	7.5 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Aspiration Pneumonia	17.5 Percent of patients	12.5 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Pain requiring narcotics	29.3 Percent of patients	30.8 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Grade 3+ Xerostomia	0 Percent of patients	0 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- feeding tube	11.8 Percent of patients	6.9 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Grade 3+ dysgeusia lasting 12 months	0 Percent of patients	0 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- osteoradionecrosis managed medically	0 Percent of patients	5 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Osteoradionecrosis requiring debridement/surgery	9.8 Percent of patients	12.5 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Lymphedema requiring referral to OT	41.0 Percent of patients	42.5 Percent of patients
Percent of Patients With Adverse Events LATE TOXICITIES- Fetal Oral Hemorrhage	0 Percent of patients	5.0 Percent of patients

SECONDARY outcome

Timeframe: 2 weeks post Radiation Therapy (RT)

Population: This outcome measure was never analyzed; data was not collected and will never be completed. Data is not available now nor will it be available in the future as the data field was not collected during the study by the original study team and the current study team has no information to analyze.

Pearson or Spearman rank based correlation between the continuous dose and perfusion summary measures

Outcome measures

Outcome data not reported

Adverse Events

Control Arm

Serious events: 15 serious events

Other events: 59 other events

Deaths: 14 deaths

Boost Arm

Serious events: 12 serious events

Other events: 38 other events

Deaths: 15 deaths

Serious adverse events

Other adverse events

Additional Information

University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin

University of Michigan Rogel Cancer Center

Phone: 734-936-9499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Control Arm n=59 participants at risk Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=41 participants at risk Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Renal and urinary disorders Acute kidney injury	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Metabolism and nutrition disorders Anorexia	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Respiratory, thoracic and mediastinal disorders Aspiration	3.4% 2/59 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Cardiac disorders Atrial fibrillation	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Constipation	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Metabolism and nutrition disorders Dehydration	3.4% 2/59 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.4% 2/59 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Fall	3.4% 2/59 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Fatigue	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Blood and lymphatic system disorders Febrile neutropenia	5.1% 3/59 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Fever	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Metabolism and nutrition disorders Hyperglycemia	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Metabolism and nutrition disorders Hyponatremia	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.4% 2/59 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Injury, poisoning and procedural complications Injury to carotid artery	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Infections and infestations Pneumonia	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Mucositis oral	3.4% 2/59 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Cardiac disorders Myocardial infarction	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Nausea	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Oral hemorrhage	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Pain	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Infections and infestations Soft tissue infection	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Nervous system disorders Syncope	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	2.4% 1/41 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Infections and infestations Tracheitis	1.7% 1/59 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Vomiting	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	7.3% 3/41 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.

Measure	Control Arm n=59 participants at risk Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy)	Boost Arm n=41 participants at risk Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy) Cisplatin: Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation Carboplatin: Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation IMRT (Intensity-Modulated Radiation Therapy) Boost Radiation to Hypoperfused Volumes
Blood and lymphatic system disorders Anemia	5.1% 3/59 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	7.3% 3/41 • Number of events 7 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Investigations Blood bilirubin increased	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Chills	5.1% 3/59 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Constipation	15.3% 9/59 • Number of events 11 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	12.2% 5/41 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Metabolism and nutrition disorders Dehydration	54.2% 32/59 • Number of events 61 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	43.9% 18/41 • Number of events 30 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Injury, poisoning and procedural complications Dermatitis radiation	79.7% 47/59 • Number of events 86 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	80.5% 33/41 • Number of events 71 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Diarrhea	11.9% 7/59 • Number of events 8 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders dry mouth	89.8% 53/59 • Number of events 169 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	82.9% 34/41 • Number of events 127 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Skin and subcutaneous tissue disorders dry skin	6.8% 4/59 • Number of events 7 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	9.8% 4/41 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Nervous system disorders Dysgeusia	91.5% 54/59 • Number of events 174 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	90.2% 37/41 • Number of events 131 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Dysphagia	88.1% 52/59 • Number of events 171 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	82.9% 34/41 • Number of events 114 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Ear and labyrinth disorders Ear Pain	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	12.2% 5/41 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Esophageal pain	22.0% 13/59 • Number of events 16 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	14.6% 6/41 • Number of events 8 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Esophagitis	44.1% 26/59 • Number of events 69 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	43.9% 18/41 • Number of events 58 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Skin and subcutaneous tissue disorders Fat atrophy	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Fatigue	59.3% 35/59 • Number of events 65 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	48.8% 20/41 • Number of events 40 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Musculoskeletal and connective tissue disorders Head soft tissue necrosis	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Mucositis oral	83.1% 49/59 • Number of events 116 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	85.4% 35/41 • Number of events 81 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Nausea	44.1% 26/59 • Number of events 44 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	43.9% 18/41 • Number of events 32 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Musculoskeletal and connective tissue disorders Neck soft tissue necrosis	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Investigations Neutrophil count decreased	10.2% 6/59 • Number of events 6 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	12.2% 5/41 • Number of events 8 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Oral pain	35.6% 21/59 • Number of events 33 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	34.1% 14/41 • Number of events 21 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
General disorders Pain	33.9% 20/59 • Number of events 33 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	29.3% 12/41 • Number of events 18 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Salivary duct inflammation	49.2% 29/59 • Number of events 100 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	51.2% 21/41 • Number of events 67 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Skin and subcutaneous tissue disorders Skin atrophy	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	9.8% 4/41 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/59 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	9.8% 4/41 • Number of events 11 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Ear and labyrinth disorders Tinnitus	8.5% 5/59 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	4.9% 2/41 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Musculoskeletal and connective tissue disorders Trismus	20.3% 12/59 • Number of events 25 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	24.4% 10/41 • Number of events 33 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Gastrointestinal disorders Vomiting	10.2% 6/59 • Number of events 7 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	22.0% 9/41 • Number of events 12 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Investigations Weight loss	40.7% 24/59 • Number of events 61 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	31.7% 13/41 • Number of events 30 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Investigations White blood cell decreased	6.8% 4/59 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	9.8% 4/41 • Number of events 9 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Nervous system disorders Headache	5.1% 3/59 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Ear and labyrinth disorders Hearing Impaired	5.1% 3/59 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Investigations Platelet count decreased	6.8% 4/59 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.
Respiratory, thoracic and mediastinal disorders Sore throat	11.9% 7/59 • Number of events 9 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.	0.00% 0/41 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 3 years.