Isotretinoin, Interferon Alfa, and Vitamin E in Treating Patients With Stage III or Stage IV Head and Neck Cancer - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00054561

Purpose

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.

Condition	Intervention	Phase
Head and Neck Cancer	Biological: recombinant interferon alfa Dietary Supplement: vitamin E Drug: isotretinoin Procedure: adjuvant therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Phase III Randomized Study of Adjuvant Biologic Therapy in Patients With Stages III/IV Head and Neck Squamous Cell Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: alpha-Tocopheryl acetate alpha-Tocopherol Interferon alfa-2a Interferon alfa-n1 Vitamin E Tocopherols Isotretinoin Tocotrienol Interferons

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	August 2003
Primary Completion Date:	December 2004 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054561

Hide Study Locations

Locations

United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300
United States, Arizona
CCOP - Mayo Clinic Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305-5216
Veterans Affairs Medical Center - Palo Alto
Palo Alto, California, United States, 94304-1290
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
MBCCOP - Howard University Cancer Center
Washington, District of Columbia, United States, 20060
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
Veterans Affairs Medical Center - Gainesville
Gainesville, Florida, United States, 32608-1197
Veterans Affairs Medical Center - Miami
Miami, Florida, United States, 33125
Veterans Affairs Medical Center - Tampa (Haley)
Tampa, Florida, United States, 33612
United States, Georgia
Veterans Affairs Medical Center - Atlanta (Decatur)
Decatur, Georgia, United States, 30033
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
CCOP - Evanston
Evanston, Illinois, United States, 60201
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615-7828
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
Veterans Affairs Medical Center - Lakeside Chicago
Chicago, Illinois, United States, 60611-4494
United States, Indiana
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
Veterans Affairs Medical Center - Indianapolis (Roudebush)
Indianapolis, Indiana, United States, 46202
United States, Iowa
Burgess Health Center
Onawa, Iowa, United States, 51040
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
John Stoddard Cancer Center at Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316-2301
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
Veterans Affairs Medical Center - Wichita
Wichita, Kansas, United States, 67218
United States, Louisiana
CCOP - Ochsner
New Orleans, Louisiana, United States, 70121
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417-2399
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
CCOP - Duluth
Duluth, Minnesota, United States, 55805
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
Midlands Cancer Center at Midlands Community Hospital
Papillion, Nebraska, United States, 68128-4157
Veterans Affairs Medical Center - Omaha
Omaha, Nebraska, United States, 68105
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
CCOP - Northern New Jersey
Hackensack, New Jersey, United States, 07601
Veterans Affairs Medical Center - East Orange
East Orange, New Jersey, United States, 07018
United States, New Mexico
MBCCOP - University of New Mexico HSC
Albuquerque, New Mexico, United States, 87131
United States, New York
Albert Einstein Clinical Cancer Center
Bronx, New York, United States, 10461
MBCCOP-Our Lady of Mercy Cancer Center
Bronx, New York, United States, 10466
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
Veterans Affairs Medical Center - Brooklyn
Brooklyn, New York, United States, 11209
Veterans Affairs Medical Center - New York
New York, New York, United States, 10010
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
CCOP - Columbus
Columbus, Ohio, United States, 43206
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
MetroHealth's Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Oklahoma
CCOP - Oklahoma
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
CCOP - MainLine Health
Wynnewood, Pennsylvania, United States, 19096
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Hahnemann University Hospital
Philadelphia, Pennsylvania, United States, 19102-1192
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15236
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Veterans Affairs Medical Center - Pittsburgh
Pittsburgh, Pennsylvania, United States, 15240
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Tennessee
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232-6307
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
Nashville, Tennessee, United States, 37212-2637
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54307-3453
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226-3596
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-0001
Veterans Affairs Medical Center - Madison
Madison, Wisconsin, United States, 53705
Veterans Affairs Medical Center - Milwaukee (Zablocki)
Milwaukee, Wisconsin, United States, 53295
Australia, New South Wales
Westmead Breast Centre at NSW Breast Cancer Institute
Westmead, New South Wales, Australia, 2145
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Peru
Instituto de Enfermedades Neoplasicas
Lima, Peru, 34
Puerto Rico
MBCCOP - San Juan
San Juan, Puerto Rico, 00921-3201
San Juan City Hospital
San Juan, Puerto Rico, 00936-7344
Veterans Affairs Medical Center - San Juan
San Juan, Puerto Rico, 00927-5800
South Africa
Pretoria Academic Hospital
Pretoria, South Africa, 0001

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Dong M. Shin, MD

Emory University

Study ID Numbers:	CDR0000271174, ECOG-1301
Study First Received:	February 5, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00054561 History of Changes
Health Authority:	United States: Federal Government