Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT00588770

Recruitment Status : Active, not recruiting

First Posted : January 9, 2008

Results First Posted : November 15, 2019

Last Update Posted : May 21, 2024

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Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Neck Squamous Cell Carcinoma of Unknown Primary Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Laryngeal Verrucous Carcinoma Recurrent Lip and Oral Cavity Squamous Cell Carcinoma Recurrent Neck Squamous Cell Carcinoma of Unknown Primary Recurrent Oral Cavity Verrucous Carcinoma Recurrent Oropharyngeal Squamous Cell Carcinoma Recurrent Salivary Gland Carcinoma Recurrent Sinonasal Squamous Cell Carcinoma Salivary Gland Squamous Cell Carcinoma Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7 Stage IV Major Salivary Gland Cancer AJCC v7 Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7 Stage IVA Laryngeal Verrucous Carcinoma AJCC v7 Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 Stage IVA Major Salivary Gland Cancer AJCC v7 Stage IVA Oral Cavity Cancer AJCC v6 and v7 Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IVA Sinonasal Squamous Cell Carcinoma AJCC v7 Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7 Stage IVB Laryngeal Verrucous Carcinoma AJCC v7 Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 Stage IVB Major Salivary Gland Cancer AJCC v7 Stage IVB Oral Cavity Cancer AJCC v6 and v7 Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IVB Sinonasal Squamous Cell Carcinoma AJCC v7 Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7 Stage IVC Laryngeal Verrucous Carcinoma AJCC v7 Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 Stage IVC Major Salivary Gland Cancer AJCC v7 Stage IVC Oral Cavity Cancer AJCC v6 and v7 Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IVC Sinonasal Squamous Cell Carcinoma AJCC v7 Tongue Carcinoma
Interventions	Biological: Bevacizumab Drug: Carboplatin Drug: Cisplatin Drug: Docetaxel Drug: Fluorouracil Other: Laboratory Biomarker Analysis
Enrollment	403

Participant Flow

Recruitment Details	E1305 was activated on August 8, 2008 and closed on February 11,2015, with final accrual of 403 patients.
Pre-assignment Details


Arm/Group Title	Chemotherapy Arm (Arm A)	Chemotherapy+Bevacizumab (Arm B)
Arm/Group Description	ARM A: Patients receive one of the ...	ARM B: Patients receive bevacizumab...
Arm/Group Description	ARM A: Patients receive one of the four chemotherapy regimens ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	ARM B: Patients receive bevacizumab in addition to the chemotherapy regimen as in arm A ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Period Title: Overall Study
Started	200	203
Eligible	188	183
Start Protocol Therapy	200	194
Completed	41	3
Not Completed	159	200
Reason Not Completed
Disease progression	85	68
Adverse Event	29	58
Death	13	22
Withdrawal by Subject	15	25
Alternative therapy	2	4
Other complicating disease	3	2
Not start protocol therapy	0	9
Lack of Efficacy	8	10
Physician discretion	2	0
Patient non-compliance	2	2

Baseline Characteristics

Arm/Group Title		Chemotherapy Arm (Arm A)	Chemotherapy+Bevacizumab (Arm B)	Total
Arm/Group Description		ARM A: Patients receive one of the ...	ARM B: Patients receive bevacizumab...	Total of all reporting groups
Arm/Group Description		ARM A: Patients receive one of the four chemotherapy regimens ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	ARM B: Patients receive bevacizumab in addition to the chemotherapy regimen as in arm A ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.	Total of all reporting groups
Overall Number of Baseline Participants		200	203	403
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All randomized patients
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	200 participants	203 participants	403 participants
		58 (32 to 86)	58 (29 to 82)	58 (29 to 86)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	200 participants	203 participants	403 participants
	Female	32 16.0%	27 13.3%	59 14.6%
	Male	168 84.0%	176 86.7%	344 85.4%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	200 participants	203 participants	403 participants
	White	168 84.0%	179 88.2%	347 86.1%
	Black	21 10.5%	18 8.9%	39 9.7%
	Other	4 2.0%	2 1.0%	6 1.5%
	Not reported	7 3.5%	4 2.0%	11 2.7%

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	Overall survival (OS) was defined as time from randomization to death ...
Description	Overall survival (OS) was defined as time from randomization to death from any course. Patients who were alive were censored at the last contact date. Median OS was estimated using the Kaplan-Meier method.
Time Frame	assessed every 3 months within 2 years from study entry, then every 6 months up to 5 years from study entry

Outcome Measure Data

Analysis Population Description

All randomized patients


Arm/Group Title	Chemotherapy Arm (Arm A)	Chemotherapy+Bevacizumab (Arm B)
Arm/Group Description:	ARM A: Patients receive one of the ...	ARM B: Patients receive bevacizumab...
Arm/Group Description:	ARM A: Patients receive one of the four chemotherapy regimens ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	ARM B: Patients receive bevacizumab in addition to the chemotherapy regimen as in arm A ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. Regimen 2: ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. Regimen 2 carbo: ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Overall Number of Participants Analyzed	200	203
Median (95% Confidence Interval) Unit of Measure: months
	11.0 (9.5 to 13.0)	12.6 (10.3 to 15.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemotherapy Arm (Arm A), Chemotherapy+Bevacizumab (Arm B)
	Comments	The study hypothesis is that the addition of bevacizumab will improve the median survival by 35% from 8.5 months (based on E1395 and E5397) to 11.5 months.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.22
	Comments	The P value was based on stratified log rank test, stratified by choice of chemotherapy combination, performance status, weight loss in the last 6 months, and prior radiation of the head and neck.
	Method	Log Rank
	Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-free Survival (PFS)
Description	Progression was defined using Response Evaluation Criteria In Solid Tu...
Description	Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression-free survival (PFS) was defined as the time from randomization to date of disease progression or death from any cause, whichever occurred first. Patients who were still alive and progression free were censored at last disease assessment date. Median PFS was estimated using Kaplan-Meier method.
Time Frame	on both arms, assessed every 2 cycles during chemotherapy treatment, then assessed every 9 weeks until progression up to 5 years from study entry; patients on arm B were assessed every 2 cycles for additional 12 weeks before changing to every 9 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients


Arm/Group Title	Chemotherapy Arm (Arm A)	Chemotherapy+Bevacizumab (Arm B)
Arm/Group Description:	ARM A: Patients receive one of the ...	ARM B: Patients receive bevacizumab...
Arm/Group Description:	ARM A: Patients receive one of the four chemotherapy regimens ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	ARM B: Patients receive bevacizumab in addition to the chemotherapy regimen as in arm A ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. Regimen 2: ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. Regimen 2 carbo: ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Overall Number of Participants Analyzed	200	203
Median (95% Confidence Interval) Unit of Measure: months
	4.3 (3.8 to 5.2)	6.0 (4.9 to 6.7)

3.Secondary Outcome


Title	Overall Response Rate
Description	Overall response rate is defined as number of patients with complete r...
Description	Overall response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all patients. Responses are evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as disappearance of target lesions or at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s).
Time Frame	on both arms, assessed every 2 cycles during chemotherapy treatment, then assessed every 9 weeks until progression up to 5 years from study entry; patients on arm B were assessed every 2 cycles for additional 12 weeks before changing to every 9 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients


Arm/Group Title	Chemotherapy Arm (Arm A)	Chemotherapy+Bevacizumab (Arm B)
Arm/Group Description:	ARM A: Patients receive one of the ...	ARM B: Patients receive bevacizumab...
Arm/Group Description:	ARM A: Patients receive one of the four chemotherapy regimens ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	ARM B: Patients receive bevacizumab in addition to the chemotherapy regimen as in arm A ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. Regimen 2: ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. Regimen 2 carbo: ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Overall Number of Participants Analyzed	200	203
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: proportion of participants
	0.245 (0.187 to 0.311)	0.355 (0.289 to 0.425)

4.Other Pre-specified Outcome


Title	To Collect Blood Samples Before and After Therapy for Future Correlative Studies
Description	These were blood and tissue samples collections and have no data to re...
Description	These were blood and tissue samples collections and have no data to report.
Time Frame	Before and after therapy

Outcome Measure Data Not Reported

5.Other Pre-specified Outcome


Title	To Collect Tumor Tissue Samples Available at Baseline From Prior Diagnostic Procedures for Future Correlative Studies
Description	These were blood and tissue samples collections and have no data to re...
Description	These were blood and tissue samples collections and have no data to report.
Time Frame	Baseline

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Assessed at the end of each cycle (1 cycle=21 days) while on treatment and at 3 months post treatment (to report late adverse events)
Adverse Event Reporting Description	At Risk for All-Cause Mortality includes all enrolled participants; at Risk for all other Adverse Events includes the safety population. A total of four chemotherapy regimen choices were allowed for the platinum-doublet treatment, and chemotherapy regimen choice was at the discretion of the treating physician and was made prior to randomization. The trial did not intent to look at the four chemotherapy regimens separately in terms of safety and efficacy.

Arm/Group Title	Chemotherapy (Arm A)	Chemotherapy + Bevacizumab (Arm B)
Arm/Group Description	ARM A: Patients receive one of the ...	ARM B: Patients receive bevacizumab...
Arm/Group Description	ARM A: Patients receive one of the four chemotherapy regimens ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	ARM B: Patients receive bevacizumab in addition to the chemotherapy regimen as in arm A ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
All-Cause Mortality
	Chemotherapy (Arm A)	Chemotherapy + Bevacizumab (Arm B)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	182/200 (91.00%)	175/203 (86.21%)
Serious Adverse Events Serious Adverse Events
	Chemotherapy (Arm A)	Chemotherapy + Bevacizumab (Arm B)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	135/199 (67.84%)	162/193 (83.94%)
Blood and lymphatic system disorders
Anemia ^† 1	17/199 (8.54%)	9/193 (4.66%)
Febrile neutropenia ^† 1	19/199 (9.55%)	35/193 (18.13%)
Cardiac disorders
Asystole ^† 1	0/199 (0.00%)	1/193 (0.52%)
Atrial fibrillation ^† 1	0/199 (0.00%)	2/193 (1.04%)
Cardiac arrest ^† 1	1/199 (0.50%)	2/193 (1.04%)
Chest pain - cardiac ^† 1	0/199 (0.00%)	1/193 (0.52%)
Left ventricular systolic dysfunction ^† 1	1/199 (0.50%)	0/193 (0.00%)
Myocardial infarction ^† 1	0/199 (0.00%)	1/193 (0.52%)
Supraventricular tachycardia ^† 1	0/199 (0.00%)	1/193 (0.52%)
Ventricular arrhythmia ^† 1	0/199 (0.00%)	1/193 (0.52%)
Ear and labyrinth disorders
Hearing impaired ^† 1	1/199 (0.50%)	1/193 (0.52%)
Tinnitus ^† 1	1/199 (0.50%)	0/193 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	1/199 (0.50%)	7/193 (3.63%)
Colitis ^† 1	0/199 (0.00%)	2/193 (1.04%)
Colonic perforation ^† 1	0/199 (0.00%)	1/193 (0.52%)
Constipation ^† 1	1/199 (0.50%)	0/193 (0.00%)
Diarrhea ^† 1	1/199 (0.50%)	9/193 (4.66%)
Duodenal hemorrhage ^† 1	0/199 (0.00%)	1/193 (0.52%)
Dyspepsia ^† 1	0/199 (0.00%)	1/193 (0.52%)
Dysphagia ^† 1	1/199 (0.50%)	9/193 (4.66%)
Esophageal fistula ^† 1	0/199 (0.00%)	2/193 (1.04%)
Esophagitis ^† 1	1/199 (0.50%)	1/193 (0.52%)
Gastric hemorrhage ^† 1	0/199 (0.00%)	3/193 (1.55%)
Gastric perforation ^† 1	0/199 (0.00%)	1/193 (0.52%)
Gastrointestinal pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Mucositis oral ^† 1	8/199 (4.02%)	37/193 (19.17%)
Nausea ^† 1	15/199 (7.54%)	22/193 (11.40%)
Oral hemorrhage ^† 1	0/199 (0.00%)	4/193 (2.07%)
Oral pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Small intestinal obstruction ^† 1	1/199 (0.50%)	1/193 (0.52%)
Stomach pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Vomiting ^† 1	9/199 (4.52%)	14/193 (7.25%)
Gastrointestinal disorders - Other ^† 1	1/199 (0.50%)	2/193 (1.04%)
General disorders
Death NOS ^† 1	1/199 (0.50%)	2/193 (1.04%)
Edema face ^† 1	1/199 (0.50%)	0/193 (0.00%)
Edema limbs ^† 1	2/199 (1.01%)	1/193 (0.52%)
Fatigue ^† 1	20/199 (10.05%)	34/193 (17.62%)
Non-cardiac chest pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Sudden death NOS ^† 1	0/199 (0.00%)	1/193 (0.52%)
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify ^† 1	0/199 (0.00%)	1/193 (0.52%)
Immune system disorders
Anaphylaxis ^† 1	1/199 (0.50%)	1/193 (0.52%)
Immune system disorders - Other, specify ^† 1	0/199 (0.00%)	1/193 (0.52%)
Infections and infestations
Abdominal infection ^† 1	0/199 (0.00%)	1/193 (0.52%)
Cranial nerve infection ^† 1	1/199 (0.50%)	0/193 (0.00%)
Enterocolitis infectious ^† 1	0/199 (0.00%)	1/193 (0.52%)
Gum infection ^† 1	0/199 (0.00%)	2/193 (1.04%)
Kidney infection ^† 1	0/199 (0.00%)	1/193 (0.52%)
Lung infection ^† 1	3/199 (1.51%)	5/193 (2.59%)
Mucosal infection ^† 1	1/199 (0.50%)	0/193 (0.00%)
Salivary gland infection ^† 1	1/199 (0.50%)	0/193 (0.00%)
Sepsis ^† 1	0/199 (0.00%)	3/193 (1.55%)
Skin infection ^† 1	2/199 (1.01%)	3/193 (1.55%)
Soft tissue infection ^† 1	0/199 (0.00%)	1/193 (0.52%)
Tracheitis ^† 1	1/199 (0.50%)	1/193 (0.52%)
Wound infection ^† 1	1/199 (0.50%)	2/193 (1.04%)
Infections and infestations - Other ^† 1	3/199 (1.51%)	6/193 (3.11%)
Injury, poisoning and procedural complications
Injury to carotid artery ^† 1	0/199 (0.00%)	1/193 (0.52%)
Tracheal hemorrhage ^† 1	0/199 (0.00%)	1/193 (0.52%)
Tracheostomy site bleeding ^† 1	0/199 (0.00%)	2/193 (1.04%)
Vascular access complication ^† 1	1/199 (0.50%)	1/193 (0.52%)
Wound dehiscence ^† 1	0/199 (0.00%)	1/193 (0.52%)
Investigations
Alanine aminotransferase increased ^† 1	1/199 (0.50%)	3/193 (1.55%)
Aspartate aminotransferase increased ^† 1	1/199 (0.50%)	1/193 (0.52%)
Creatinine increased ^† 1	1/199 (0.50%)	2/193 (1.04%)
Lymphocyte count decreased ^† 1	12/199 (6.03%)	12/193 (6.22%)
Neutrophil count decreased ^† 1	53/199 (26.63%)	73/193 (37.82%)
Platelet count decreased ^† 1	13/199 (6.53%)	15/193 (7.77%)
Weight loss ^† 1	4/199 (2.01%)	5/193 (2.59%)
White blood cell decreased ^† 1	33/199 (16.58%)	51/193 (26.42%)
Investigations - Other, specify ^† 1	1/199 (0.50%)	0/193 (0.00%)
Metabolism and nutrition disorders
Anorexia ^† 1	13/199 (6.53%)	12/193 (6.22%)
Dehydration ^† 1	11/199 (5.53%)	30/193 (15.54%)
Hypoalbuminemia ^† 1	0/199 (0.00%)	1/193 (0.52%)
Hypocalcemia ^† 1	2/199 (1.01%)	2/193 (1.04%)
Hypokalemia ^† 1	8/199 (4.02%)	5/193 (2.59%)
Hypomagnesemia ^† 1	1/199 (0.50%)	1/193 (0.52%)
Hyponatremia ^† 1	5/199 (2.51%)	7/193 (3.63%)
Hypophosphatemia ^† 1	1/199 (0.50%)	6/193 (3.11%)
Metabolism and nutrition - Other ^† 1	0/199 (0.00%)	1/193 (0.52%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/199 (0.00%)	1/193 (0.52%)
Back pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Bone pain ^† 1	1/199 (0.50%)	1/193 (0.52%)
Generalized muscle weakness ^† 1	1/199 (0.50%)	4/193 (2.07%)
Muscle weakness lower limb ^† 1	0/199 (0.00%)	1/193 (0.52%)
Myalgia ^† 1	0/199 (0.00%)	2/193 (1.04%)
Neck pain ^† 1	0/199 (0.00%)	1/193 (0.52%)
Osteonecrosis of jaw ^† 1	0/199 (0.00%)	2/193 (1.04%)
Pain in extremity ^† 1	0/199 (0.00%)	1/193 (0.52%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms - Other ^† 1	0/199 (0.00%)	2/193 (1.04%)
Nervous system disorders
Ataxia ^† 1	0/199 (0.00%)	1/193 (0.52%)
Dizziness ^† 1	0/199 (0.00%)	1/193 (0.52%)
Peripheral motor neuropathy ^† 1	0/199 (0.00%)	2/193 (1.04%)
Peripheral sensory neuropathy ^† 1	4/199 (2.01%)	4/193 (2.07%)
Reversible posterior leukoencephalopathy ^† 1	0/199 (0.00%)	1/193 (0.52%)
Seizure ^† 1	0/199 (0.00%)	1/193 (0.52%)
Syncope ^† 1	3/199 (1.51%)	5/193 (2.59%)
Nervous system disorders - Other ^† 1	0/199 (0.00%)	2/193 (1.04%)
Psychiatric disorders
Confusion ^† 1	0/199 (0.00%)	1/193 (0.52%)
Depression ^† 1	1/199 (0.50%)	0/193 (0.00%)
Renal and urinary disorders
Acute kidney injury ^† 1	3/199 (1.51%)	3/193 (1.55%)
Proteinuria ^† 1	0/199 (0.00%)	3/193 (1.55%)
Renal and urinary disorders - Other ^† 1	0/199 (0.00%)	1/193 (0.52%)
Respiratory, thoracic and mediastinal disorders
Aspiration ^† 1	0/199 (0.00%)	1/193 (0.52%)
Bronchopulmonary hemorrhage ^† 1	0/199 (0.00%)	1/193 (0.52%)
Dyspnea ^† 1	1/199 (0.50%)	1/193 (0.52%)
Hiccups ^† 1	1/199 (0.50%)	0/193 (0.00%)
Hoarseness ^† 1	0/199 (0.00%)	1/193 (0.52%)
Hypoxia ^† 1	1/199 (0.50%)	0/193 (0.00%)
Laryngeal edema ^† 1	0/199 (0.00%)	1/193 (0.52%)
Laryngeal hemorrhage ^† 1	1/199 (0.50%)	1/193 (0.52%)
Laryngeal mucositis ^† 1	0/199 (0.00%)	2/193 (1.04%)
Pharyngeal fistula ^† 1	0/199 (0.00%)	1/193 (0.52%)
Pharyngeal hemorrhage ^† 1	0/199 (0.00%)	1/193 (0.52%)
Pharyngeal mucositis ^† 1	1/199 (0.50%)	1/193 (0.52%)
Pharyngolaryngeal pain ^† 1	4/199 (2.01%)	5/193 (2.59%)
Pleural effusion ^† 1	0/199 (0.00%)	1/193 (0.52%)
Pneumonitis ^† 1	0/199 (0.00%)	2/193 (1.04%)
Pneumothorax ^† 1	0/199 (0.00%)	1/193 (0.52%)
Respiratory failure ^† 1	0/199 (0.00%)	2/193 (1.04%)
Respiratory thoracic mediastinal - Other ^† 1	2/199 (1.01%)	0/193 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	1/199 (0.50%)	0/193 (0.00%)
Pain of skin ^† 1	0/199 (0.00%)	1/193 (0.52%)
Palmar-plantar erythrodysesthesia ^† 1	2/199 (1.01%)	0/193 (0.00%)
Rash maculo-papular ^† 1	1/199 (0.50%)	0/193 (0.00%)
Vascular disorders
Hypertension ^† 1	0/199 (0.00%)	12/193 (6.22%)
Hypotension ^† 1	3/199 (1.51%)	4/193 (2.07%)
Thromboembolic event ^† 1	1/199 (0.50%)	10/193 (5.18%)
1 Term from vocabulary, CTCAE 4.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Chemotherapy (Arm A)	Chemotherapy + Bevacizumab (Arm B)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	50/199 (25.13%)	50/193 (25.91%)
General disorders
Fatigue ^† 1	13/199 (6.53%)	19/193 (9.84%)
Investigations
Platelet count decreased ^† 1	9/199 (4.52%)	10/193 (5.18%)
Metabolism and nutrition disorders
Anorexia ^† 1	6/199 (3.02%)	13/193 (6.74%)
Nervous system disorders
Peripheral sensory neuropathy ^† 1	28/199 (14.07%)	24/193 (12.44%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	19/199 (9.55%)	11/193 (5.70%)
1 Term from vocabulary, CTCAE 4.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Study statistician
Organization:	ECOG-ACRIN Cancer Reserch Group Statistical Office
Phone:	6176323012
EMail:	eatrials@jimmy.harvard.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Argiris A, Li S, Savvides P, Ohr JP, Gilbert J, Levine MA, Chakravarti A, Haigentz M Jr, Saba NF, Ikpeazu CV, Schneider CJ, Pinto HA, Forastiere AA, Burtness B. Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer. J Clin Oncol. 2019 Dec 1;37(34):3266-3274. doi: 10.1200/JCO.19.00555. Epub 2019 Oct 16.

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00588770
Other Study ID Numbers:	NCI-2009-00507 NCI-2009-00507 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) E1305 CDR0000582533 E1305 ( Other Identifier: ECOG-ACRIN Cancer Research Group ) E1305 ( Other Identifier: CTEP ) U10CA180820 ( U.S. NIH Grant/Contract ) U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted:	December 28, 2007
First Posted:	January 9, 2008
Results First Submitted:	September 18, 2019
Results First Posted:	November 15, 2019
Last Update Posted:	May 21, 2024

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