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

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

Sponsoren

Hauptsponsor: Eastern Cooperative Oncology Group

Mitarbeiter: National Cancer Institute (NCI)

Quelle Eastern Cooperative Oncology Group
Kurze Zusammenfassung

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.

detaillierte Beschreibung

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.

Gesamtstatus Completed
Anfangsdatum August 2003
Fertigstellungstermin May 1, 2009
Primäres Abschlussdatum December 2004
Phase Phase 3
Studientyp Interventional
Bedingung
Intervention

Interventionsart: Biological

Interventionsname: recombinant interferon alfa

Interventionsart: Dietary Supplement

Interventionsname: vitamin E

Interventionsart: Drug

Interventionsname: isotretinoin

Interventionsart: Procedure

Interventionsname: adjuvant therapy

Teilnahmeberechtigung

Kriterien:

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

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: 120 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Dong M. Shin, MD Study Chair Emory University
Ort
Einrichtung:
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
Standort Länder

Australia

Peru

Puerto Rico

South Africa

United States

Überprüfungsdatum

December 2018

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Studiendesign Info

Zuweisung: Randomized

Hauptzweck: Treatment

Quelle: ClinicalTrials.gov