Phase III Randomized Study of Adjuvant Biologic Therapy in Patients With Stages III/IV Head and Neck Squamous Cell Carcinoma
Isotretinoin, Interferon Alfa, and Vitamin E in Treating Patients With Stage III or Stage IV Head and Neck Cancer
Sponsors
Source
Eastern Cooperative Oncology Group
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
Brief Summary
RATIONALE: Drugs used in chemotherapy such as isotretinoin use different ways to stop tumor
cells from dividing so they stop growing or die. Interferon alfa may interfere with the
growth of tumor cells. Vitamin E may be able to decrease side effects caused by isotretinoin.
It is not yet known whether combining isotretinoin and interferon alfa with vitamin E is more
effective than observation in preventing recurrence of head and neck cancer after surgery
and/or radiation therapy.
PURPOSE: Randomized phase III trial to compare the effectiveness of isotretinoin and
interferon alfa combined with vitamin E with that of observation in treating patients who
have undergone surgery and/or radiation therapy for stage III or stage IV head and neck
cancer.
Detailed Description
OBJECTIVES:
- Determine the efficacy of adjuvant isotretinoin, interferon alfa, and vitamin E, in
terms of incidence of primary disease recurrence and secondary primary tumor
development, in patients with stage III or IV squamous cell carcinoma of the head and
neck previously treated with definitive surgical excision and/or postoperative
radiotherapy.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
- Compare the overall and disease-free survival of patients treated with this regimen vs
those who undergo observation only.
- Determine whether alterations of p53 gene, retinoic acid receptors, retinoid-regulated
gene, and interferon-responsive genes are associated with clinical outcome in these
patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T
stage (T1 or T2 vs T3 or T4), N stage (N0 or N1 vs N2 or N3), prior therapy (complete tumor
resection vs resection and radiotherapy/chemoradiotherapy vs radiotherapy or
chemoradiotherapy alone), and prior chemotherapy (yes vs no). Patients are randomized to 1 of
2 treatment arms.
- Arm I: Patients receive oral isotretinoin once daily, interferon alfa subcutaneously 3
times weekly, and oral vitamin E 3 times daily. Treatment repeats every month for 12
courses (1 year) in the absence of disease recurrence or unacceptable toxicity.
- Arm II: Patients undergo observation only for 1 year. Patients are followed every 3
months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 376 patients (188 per treatment arm) will be accrued for this
study within 3.75 years.
Overall Status
Completed
Start Date
2003-08-01
Completion Date
2009-05-01
Primary Completion Date
2004-12-01
Phase
Phase 3
Study Type
Interventional
Condition
Intervention
Eligibility
Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed squamous cell carcinoma of the head and neck
- Primary site must be within the oral cavity, oropharynx, larynx, or hypopharynx
- Stage III or IV primary lesion at diagnosis
- No distant metastatic disease at diagnosis
- No multiple primary lesions
- Currently disease-free after treatment with 1 of the following:
- Complete tumor resection
- Radiotherapy or chemoradiotherapy alone*
- Resection followed by radiotherapy/chemoradiotherapy*
- No more than 4-16 weeks since prior surgery and/or radiotherapy/chemoradiotherapy
NOTE: *Radiotherapy must have been 70-72 Gy in 1.8-2.0 Gy fractions to the primary
tumor and clinically positive neck nodes and 44-50 Gy in 1.8-2.0 Gy fractions to
clinically negative nodes, including the lower neck
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin no greater than 1.5 mg/dL
- AST and ALT no greater than 2 times upper limit of normal (ULN)
- Alkaline phosphatase no greater than 2 times ULN
Renal
- Creatinine no greater than 1.2 mg/dL
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 1 month prior to, during, and
for 1 month after study therapy
- Electrolytes normal
- Fasting serum triglyceride level no greater than 2 times ULN (anti-triglyceride
medication allowed)
- No other malignancy within the past 2 years except localized basal cell or squamous
cell skin cancer
- No other concurrent medical condition that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy and recovered
- Prior neoadjuvant chemotherapy allowed
- Prior chemotherapy administered concurrently with radiotherapy allowed
- No other concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- See Disease Characteristics
- Recovered from prior radiotherapy
Surgery
- See Disease Characteristics
- Recovered from prior surgery
Other
- No history of megadose vitamin A (more than 25,000 I.U.)
- No other clinical trial enrollment that would preclude adjuvant systemic therapy
- No concurrent vitamin supplements containing vitamin A
Gender
All
Minimum Age
18 Years
Maximum Age
120 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Dong M. Shin, MD |
Study Chair |
Emory University |
Location
Facility |
University of Alabama at Birmingham Comprehensive Cancer Center Birmingham Alabama 35294-3300 United States |
CCOP - Mayo Clinic Scottsdale Oncology Program Scottsdale Arizona 85259-5404 United States |
City of Hope Comprehensive Cancer Center Duarte California 91010-3000 United States |
Veterans Affairs Medical Center - Palo Alto Palo Alto California 94304-1290 United States |
Stanford Cancer Center at Stanford University Medical Center Stanford California 94305-5216 United States |
CCOP - Christiana Care Health Services Newark Delaware 19713 United States |
MBCCOP - Howard University Cancer Center Washington District of Columbia 20060 United States |
Veterans Affairs Medical Center - Gainesville Gainesville Florida 32608-1197 United States |
Veterans Affairs Medical Center - Miami Miami Florida 33125 United States |
H. Lee Moffitt Cancer Center and Research Institute Tampa Florida 33612-9497 United States |
Veterans Affairs Medical Center - Tampa (Haley) Tampa Florida 33612 United States |
Winship Cancer Institute of Emory University Atlanta Georgia 30322 United States |
Veterans Affairs Medical Center - Atlanta (Decatur) Decatur Georgia 30033 United States |
Veterans Affairs Medical Center - Lakeside Chicago Chicago Illinois 60611-4494 United States |
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois 60611 United States |
CCOP - Central Illinois Decatur Illinois 62526 United States |
Decatur Memorial Hospital Cancer Care Institute Decatur Illinois 62526 United States |
CCOP - Evanston Evanston Illinois 60201 United States |
CCOP - Illinois Oncology Research Association Peoria Illinois 61615-7828 United States |
CCOP - Carle Cancer Center Urbana Illinois 61801 United States |
Indiana University Cancer Center Indianapolis Indiana 46202-5289 United States |
Veterans Affairs Medical Center - Indianapolis (Roudebush) Indianapolis Indiana 46202 United States |
CCOP - Northern Indiana CR Consortium South Bend Indiana 46601 United States |
CCOP - Cedar Rapids Oncology Project Cedar Rapids Iowa 52403-1206 United States |
CCOP - Iowa Oncology Research Association Des Moines Iowa 50309-1016 United States |
John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines Iowa 50309 United States |
Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines Iowa 50314 United States |
John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines Iowa 50316-2301 United States |
Burgess Health Center Onawa Iowa 51040 United States |
CCOP - Wichita Wichita Kansas 67214-3882 United States |
Veterans Affairs Medical Center - Wichita Wichita Kansas 67218 United States |
MBCCOP - LSU Health Sciences Center New Orleans Louisiana 70112 United States |
CCOP - Ochsner New Orleans Louisiana 70121 United States |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland 21231 United States |
Tufts - New England Medical Center Boston Massachusetts 02111 United States |
Beth Israel Deaconess Medical Center Boston Massachusetts 02215 United States |
CCOP - Michigan Cancer Research Consortium Ann Arbor Michigan 48106 United States |
CCOP - Kalamazoo Kalamazoo Michigan 49007-3731 United States |
West Michigan Cancer Center Kalamazoo Michigan 49007 United States |
CCOP - Duluth Duluth Minnesota 55805 United States |
Veterans Affairs Medical Center - Minneapolis Minneapolis Minnesota 55417-2399 United States |
University of Minnesota Cancer Center Minneapolis Minnesota 55455 United States |
Mayo Clinic Cancer Center Rochester Minnesota 55905 United States |
CCOP - Metro-Minnesota Saint Louis Park Minnesota 55416 United States |
Veterans Affairs Medical Center - Omaha Omaha Nebraska 68105 United States |
CCOP - Missouri Valley Cancer Consortium Omaha Nebraska 68106 United States |
Midlands Cancer Center at Midlands Community Hospital Papillion Nebraska 68128-4157 United States |
CCOP - Southern Nevada Cancer Research Foundation Las Vegas Nevada 89106 United States |
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon New Hampshire 03756-0002 United States |
Veterans Affairs Medical Center - East Orange East Orange New Jersey 07018 United States |
CCOP - Northern New Jersey Hackensack New Jersey 07601 United States |
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital New Brunswick New Jersey 08903 United States |
MBCCOP - University of New Mexico HSC Albuquerque New Mexico 87131 United States |
Albert Einstein Clinical Cancer Center Bronx New York 10461 United States |
MBCCOP-Our Lady of Mercy Cancer Center Bronx New York 10466 United States |
Veterans Affairs Medical Center - Brooklyn Brooklyn New York 11209 United States |
Veterans Affairs Medical Center - New York New York New York 10010 United States |
NYU School of Medicine's Kaplan Comprehensive Cancer Center New York New York 10016 United States |
CCOP - Merit Care Hospital Fargo North Dakota 58122 United States |
MetroHealth's Cancer Care Center at MetroHealth Medical Center Cleveland Ohio 44109 United States |
Cleveland Clinic Taussig Cancer Center Cleveland Ohio 44195 United States |
CCOP - Columbus Columbus Ohio 43206 United States |
CCOP - Toledo Community Hospital Toledo Ohio 43623-3456 United States |
CCOP - Oklahoma Tulsa Oklahoma 74136 United States |
CCOP - Geisinger Clinic and Medical Center Danville Pennsylvania 17822-2001 United States |
Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania 17033-0850 United States |
Hahnemann University Hospital Philadelphia Pennsylvania 19102-1192 United States |
Abramson Cancer Center of the University of Pennsylvania Philadelphia Pennsylvania 19104 United States |
Fox Chase Cancer Center Philadelphia Pennsylvania 19111-2497 United States |
Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania 15236 United States |
Veterans Affairs Medical Center - Pittsburgh Pittsburgh Pennsylvania 15240 United States |
CCOP - MainLine Health Wynnewood Pennsylvania 19096 United States |
CCOP - Sioux Community Cancer Consortium Sioux Falls South Dakota 57104 United States |
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus Nashville Tennessee 37212-2637 United States |
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center Nashville Tennessee 37232-6307 United States |
CCOP - Scott and White Hospital Temple Texas 76508 United States |
CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay Wisconsin 54307-3453 United States |
Veterans Affairs Medical Center - Madison Madison Wisconsin 53705 United States |
University of Wisconsin Comprehensive Cancer Center Madison Wisconsin 53792-0001 United States |
CCOP - Marshfield Clinic Research Foundation Marshfield Wisconsin 54449 United States |
Medical College of Wisconsin Cancer Center Milwaukee Wisconsin 53226-3596 United States |
Veterans Affairs Medical Center - Milwaukee (Zablocki) Milwaukee Wisconsin 53295 United States |
Westmead Breast Centre at NSW Breast Cancer Institute Westmead New South Wales 2145 Australia |
Westmead Hospital Westmead New South Wales 2145 Australia |
Instituto de Enfermedades Neoplasicas Lima 34 Peru |
MBCCOP - San Juan San Juan 00921-3201 Puerto Rico |
Veterans Affairs Medical Center - San Juan San Juan 00927-5800 Puerto Rico |
San Juan City Hospital San Juan 00936-7344 Puerto Rico |
Pretoria Academic Hospital Pretoria 0001 South Africa |
Location Countries
Country
Australia
Peru
Puerto Rico
South Africa
United States
Verification Date
2018-12-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Keywords
stage III squamous cell carcinoma of the lip and oral cavity
, stage IV squamous cell carcinoma of the lip and oral cavity
, stage III squamous cell carcinoma of the oropharynx
, stage IV squamous cell carcinoma of the oropharynx
, stage III squamous cell carcinoma of the larynx
, stage IV squamous cell carcinoma of the larynx
, stage III squamous cell carcinoma of the hypopharynx
, stage IV squamous cell carcinoma of the hypopharynx 








Has Expanded Access
No
Condition Browse
Secondary Id
ECOG-1301
Intervention Browse
Mesh Term
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Interferons
Interferon-alpha
Isotretinoin
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Primary Purpose
Treatment
Study First Submitted
February 5, 2003
Study First Submitted Qc
February 5, 2003
Study First Posted
February 6, 2003
Last Update Submitted
December 30, 2018
Last Update Submitted Qc
December 30, 2018
Last Update Posted
January 1, 2019
ClinicalTrials.gov processed this data on December 11, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.