Trial Outcomes & Findings for Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer (NCT NCT01566435)

NCT ID: NCT01566435

Last Updated: 2020-10-01

Results Overview

* Response will be assessed by laryngoscopy. * CR: disappearance of all lesions

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

6 weeks (2 cycles of therapy)

Results posted on

2020-10-01

Participant Flow

The study opened to participant enrollment on 08/09/2012 and closed to participant enrollment on 11/07/2013.

Participant milestones

Participant milestones
Measure	Arm 1-ACF Induction Therapy Followed by Chemoradiation Therapy ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) * nab-Paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 * Cisplatin 75 mg/m\^2 on Day 1 * 5-FU 750 mg/m\^2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy * Cisplatin 100 mg/m\^2 IV on Days 1, 22, and 43 * Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. * If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m\^2 IV week for 8 weeks
ACF Induction Therapy STARTED	30
ACF Induction Therapy COMPLETED	30
ACF Induction Therapy NOT COMPLETED	0
ACF Definitive Chemoradiation-cisplatin STARTED	28
ACF Definitive Chemoradiation-cisplatin COMPLETED	27
ACF Definitive Chemoradiation-cisplatin NOT COMPLETED	1
ACF Definitive Chemoradiation-cetuximab STARTED	2
ACF Definitive Chemoradiation-cetuximab COMPLETED	2
ACF Definitive Chemoradiation-cetuximab NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1-ACF Induction Therapy Followed by Chemoradiation Therapy ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) * nab-Paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 * Cisplatin 75 mg/m\^2 on Day 1 * 5-FU 750 mg/m\^2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy * Cisplatin 100 mg/m\^2 IV on Days 1, 22, and 43 * Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. * If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m\^2 IV week for 8 weeks
ACF Definitive Chemoradiation-cisplatin Withdrawal by Subject	1

Baseline Characteristics

Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1-ACF Induction Therapy Followed by Chemoradiation Therapy n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Age, Continuous	58.8 years n=99 Participants
Sex: Female, Male Female	5 Participants n=99 Participants
Sex: Female, Male Male	25 Participants n=99 Participants
Region of Enrollment United States	30 participants n=99 Participants
Smoking history Yes	23 participants n=99 Participants
Smoking history No	7 participants n=99 Participants
T Stage T2	8 participants n=99 Participants
T Stage T3	13 participants n=99 Participants
T Stage T4	9 participants n=99 Participants
Primary tumor site Oropharynx	18 participants n=99 Participants
Primary tumor site Larynx	9 participants n=99 Participants
Primary tumor site Hypopharynx	3 participants n=99 Participants
HPV Status HPV-related OPSCC	17 participants n=99 Participants
HPV Status HPV-unrelated HNSCC	13 participants n=99 Participants
Overall stage of disease III	3 participants n=99 Participants
Overall stage of disease IVA	18 participants n=99 Participants
Overall stage of disease IVB	9 participants n=99 Participants

PRIMARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

* Response will be assessed by laryngoscopy. * CR: disappearance of all lesions

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Percentage of Participants With Complete Response (CR) by Clinical Exam at Primary Tumor Site	76.7 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

* Response will be assessed by laryngoscopy. * PR: at least 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Percentage of Participants With Partial Response (PR) at Primary Tumor Site	16.7 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

* Response assessed using RECIST criteria version 1.0 * Complete response: disappearance of all target lesions * Partial response: at least 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter * Non-complete response/non-progression: persistence of one or more non-target lesion and/or maintenance of tumor marker level above the upper limits of normal. * Progression: at least a 20% increase in the sum of the LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Number of Participants Per Anatomic Tumor Response by CT Scan Complete response	23 participants
Number of Participants Per Anatomic Tumor Response by CT Scan Partial response	5 participants
Number of Participants Per Anatomic Tumor Response by CT Scan Non-complete response/Non-progression/Progression	2 participants

SECONDARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

Population: 29 participants out of 30 participants were evaluable for this outcome measure.

* Complete metabolic response (CMR): Complete resolution of all metabolically active target and non-target lesions, and no interval development of new lesions * Partial metabolic response (PMR): 20% or greater decrease in max SUV from baseline, no metabolic progression of non-target lesions and no new lesions and/or decrease in total number of non-target lesions, no new lesions * Stable metabolic disease (SMD) - does not qualify for CMR, PMR, or PMD * Progressive metabolic disease (PMD): development of one or more metabolically active lesions or 20% or greater increased in max SUV from baseline, new metabolically active lesions

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=29 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Metabolic Tumor Responses as Measured by FDG-PET/CT Complete metabolic response	3 participants
Metabolic Tumor Responses as Measured by FDG-PET/CT Partial metabolic response rate	25 participants
Metabolic Tumor Responses as Measured by FDG-PET/CT Stable or Progressive Metabolic Disease	1 participants

SECONDARY outcome

Timeframe: 2 years

-Overall survival rate is the percentage of participants who are alive at 2 years.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Overall Survival Rate	93.0 percentage of participants

SECONDARY outcome

Timeframe: From start of treatment through 30 days after end of treatment

Assessed by NCI-CTCAE version 3

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Neutropenia	9 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Neutropenia	7 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Thrombocytopenia	11 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades1/2 Anemia	24 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Anemia	2 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Tinnitus	3 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Tinnitus	1 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Rash	5 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Diarrhea	9 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Diarrhea	3 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Mucositis	8 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Mucositis	1 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Febrile Neutropenia	4 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Edema: Limb	5 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Creatinine	7 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 ALT	4 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 ALT	1 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 AST	2 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 AST	1 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Sensory Neuropathy-peripheral	4 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Sensory Neuropathy - peripheral	1 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Fatigue	13 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Fatigue	1 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 1/2 Weight Loss	7 participants
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy Grades 3/4 Weight Loss	6 participants

SECONDARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

Population: The data was not collected for this outcome measure.

SPARC and Ki-67 expression will be assessed at this institution by IHC stains performed on clinically available tumor specimens (paraffin blocks). The specimens will be collected retrospectively from prior biopsies (pre treatment and following 2 cycles of ACF) that will have consisted of a minimum of two needle cores (16-18 gauge) or two small incisional/excisional pieces of tumor. These will have been placed in 2% buffered formalin and transported to the surgical pathology processing lab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

Population: 2 participants were not evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=28 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Complete Response (CR) or Partial Response (PR) at Regional (Neck) Nodes as Measured by Clinical Exam Complete response	19 participants
Complete Response (CR) or Partial Response (PR) at Regional (Neck) Nodes as Measured by Clinical Exam Partial response	7 participants

SECONDARY outcome

Timeframe: 6 weeks (2 cycles of therapy)

Population: The data was not collected for this outcome measure.

Ki-67 expression will be assessed at this institution by IHC stains performed on clinically available tumor specimens (paraffin blocks). The specimens will be collected retrospectively from prior biopsies (pre treatment and following 2 cycles of ACF) that will have consisted of a minimum of two needle cores (16-18 gauge) or two small incisional/excisional pieces of tumor. These will have been placed in 2% buffered formalin and transported to the surgical pathology processing lab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Disease-free Survival (DFS) Rate	97.0 percentage of participants

SECONDARY outcome

Timeframe: 2 years

-Progression: at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Progression-free Survival (PFS)	97 percentage of participants

SECONDARY outcome

Timeframe: Through one year after completion of treatment

Population: Questionnaires were not collected at some time points due to various reasons including patient decision, death, lost to follow-up, and missed by staff.

* Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck * Scored from 0 (not at all) to 4 (very much) * Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being * The FACT-H\&N Total Score (range 0-148) measures the sum of the physical, social, emotional, functional, and HNCS domains * The maximum score of 148 reflects the best quality of life.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score End of chemoradiation treatment	74.2 score on a scale Interval 67.1 to 81.3
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score 3 months after completion of treatment	98.4 score on a scale Interval 88.0 to 108.7
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score 6 months after completion of treatment	107.4 score on a scale Interval 95.7 to 119.2
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score 12 months after completion of treatment	114.6 score on a scale Interval 105.1 to 124.1
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score Baseline	109.7 score on a scale Interval 99.6 to 119.8
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score End of induction	105.8 score on a scale Interval 96.2 to 115.4

SECONDARY outcome

Timeframe: Through end of chemoradiation

Population: Questionnaires were not collected at some time points due to various reasons including patient decision, death, lost to follow-up, and missed by staff.

* Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck * Scored from 0 (not at all) to 4 (very much) * Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being * The FACT-G Total Score (range 0-108) measures the sum of the physical, social, emotional, and functional domains but excludes the HNCS domain * The maximum score of 108 reflects the best quality of life.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) FACT-G Total Score Baseline	83.8 score on a scale Interval 77.1 to 90.3
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) FACT-G Total Score End of induction	79.1 score on a scale Interval 72.3 to 85.7
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) FACT-G Total Score End of chemoradiation treatment	62.3 score on a scale Interval 57.0 to 67.5

SECONDARY outcome

Timeframe: Through end of chemoradiation

Population: Questionnaires were not collected at some time points due to various reasons including patient decision, death, lost to follow-up, and missed by staff.

* Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck * Scored from 0 (not at all) to 4 (very much) * Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being * The FACT-H\&N TOI (range 0-96) measures the total score for the physical, functional, and HNCS domains but excludes the emotional and social domains * The maximum score of 96 reflects the best quality of life.

Outcome measures

Outcome measures
Measure	Arm 1 (ACF) n=30 Participants ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m2 on Day 1 3. 5-FU 750 mg/m2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy 1. Cisplatin 100 mg/m2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions. 3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m2 IV week for 8 weeks
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Trial Outcome Index (TOI) Baseline	69.7 score on a scale Interval 62.0 to 77.5
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Trial Outcome Index (TOI) End of induction	62.3 score on a scale Interval 54.8 to 69.8
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Trial Outcome Index (TOI) End of chemoradiation treatment	34.2 score on a scale Interval 28.3 to 40.1

Adverse Events

ACF Induction Therapy

Serious events: 15 serious events

Other events: 30 other events

Deaths: 0 deaths

ACF Definitive Chemoradiation Therapy-cisplatin

Serious events: 4 serious events

Other events: 27 other events

Deaths: 0 deaths

ACF Definitive Chemoradiation Therapy-cetuximab

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Douglas Adkins, M.D.

Washington University School of Medicine

Phone: 314-747-7402

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ACF Induction Therapy n=30 participants at risk ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks) 1. nab-Paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 2. Cisplatin 75 mg/m\^2 on Day 1 3. 5-FU 750 mg/m\^2 on Days 1-3 If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF.	ACF Definitive Chemoradiation Therapy-cisplatin n=27 participants at risk Definitive Therapy 1. Cisplatin 100 mg/m\^2 IV on Days 1, 22, and 43 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions.	ACF Definitive Chemoradiation Therapy-cetuximab n=2 participants at risk Definitive Therapy 1. Cetuximab 250 mg/m\^2 IV weekly for 8 weeks 2. Intensity modulated radiation therapy (IMRT) 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions.
Investigations ALT	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Investigations AST	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Respiratory, thoracic and mediastinal disorders Aspiration pneumonia	0.00% 0/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Cardiac disorders Atrial fibrillation	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Psychiatric disorders Confusion	0.00% 0/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Renal and urinary disorders Creatinine	0.00% 0/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Metabolism and nutrition disorders Dehydration	6.7% 2/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Gastrointestinal disorders Diarrhea	10.0% 3/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Gastrointestinal disorders Dysphagia	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
General disorders Fatigue	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Infections and infestations Febrile neutropenia	10.0% 3/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Renal and urinary disorders Hematuria	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Blood and lymphatic system disorders Hemoglobin (Anemia)	6.7% 2/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Metabolism and nutrition disorders Hyperglycemia	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Metabolism and nutrition disorders Hypoalbuminemia	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Metabolism and nutrition disorders Hypokalemia	16.7% 5/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Metabolism and nutrition disorders Hyponatremia	13.3% 4/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Metabolism and nutrition disorders Hypophosphatemia	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Cardiac disorders Hypotension	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Infections and infestations Infection with grade 3 or 4 neutrophils	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Investigations Leukopenia	26.7% 8/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Investigations Lymphopenia	13.3% 4/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Gastrointestinal disorders Mucositis	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Cardiac disorders Myocardial infarction	0.00% 0/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Investigations Neutrophils (Neutropenia)	20.0% 6/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Nervous system disorders Peripheral sensory neuropathy	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Infections and infestations Platelets (Thrombocytopenia)	0.00% 0/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Renal and urinary disorders Renal failure	0.00% 0/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	3.7% 1/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Infections and infestations Skin (cellulitis)	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Gastrointestinal disorders Taste alteration	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Vascular disorders Thrombosis/thrombus/embolism	6.7% 2/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
Gastrointestinal disorders Vomiting	3.3% 1/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.
General disorders Weight loss	23.3% 7/30 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/27 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.	0.00% 0/2 Serious adverse events are all grade 3, 4, or 5 anticipated or unanticipated events per CTCAE Version 3.0.