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

Head and Neck Cancer Clinical Trial

Official title:

Phase III Randomized Study of Adjuvant Biologic Therapy in Patients With Stages III/IV Head and Neck Squamous Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054561
• Other study ID #: CDR0000271174
• Secondary ID: ECOG-1301
• Status: Completed
• Phase: Phase 3
• Start date: November 26, 2003
• Est. completion date: May 1, 2009

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: May 1, 2009
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• recombinant interferon alfa

Dietary Supplement:
• vitamin E

Drug:
• isotretinoin

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
Australia	Westmead Breast Centre at NSW Breast Cancer Institute	Westmead	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Peru	Instituto de Enfermedades Neoplasicas	Lima
Puerto Rico	MBCCOP - San Juan	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	Veterans Affairs Medical Center - San Juan	San Juan
South Africa	Pretoria Academic Hospital	Pretoria
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	Albert Einstein Clinical Cancer Center	Bronx	New York
United States	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York
United States	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	MetroHealth's Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Central Illinois	Decatur	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Veterans Affairs Medical Center - Gainesville	Gainesville	Florida
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Veterans Affairs Medical Center - Miami	Miami	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee
United States	Cancer Institute of New Jersey at Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Veterans Affairs Medical Center - New York	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Veterans Affairs Medical Center - Omaha	Omaha	Nebraska
United States	Burgess Health Center	Onawa	Iowa
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Midlands Cancer Center at Midlands Community Hospital	Papillion	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Veterans Affairs Medical Center - Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Peru,  Puerto Rico,  South Africa,