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

Sponsor
Eastern Cooperative Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00054561
Collaborator
National Cancer Institute (NCI) (NIH)
89
Locations
69
Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: recombinant interferon alfa
  • Dietary Supplement: vitamin E
  • Drug: isotretinoin
  • Procedure: adjuvant therapy
 Phase 3

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.

Study Design

Study Type:
Interventional
Allocation:
Randomized
Primary Purpose:
Treatment
Official Title:
Phase III Randomized Study of Adjuvant Biologic Therapy in Patients With Stages III/IV Head and Neck Squamous Cell Carcinoma
Actual Study Start Date :
Aug 1, 2003
Actual Primary Completion Date :
Dec 1, 2004
Actual Study Completion Date :
May 1, 2009

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 120 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Comprehensive Cancer Center Birmingham Alabama United States 35294-3300
    2 CCOP - Mayo Clinic Scottsdale Oncology Program Scottsdale Arizona United States 85259-5404
    3 City of Hope Comprehensive Cancer Center Duarte California United States 91010-3000
    4 Veterans Affairs Medical Center - Palo Alto Palo Alto California United States 94304-1290
    5 Stanford Cancer Center at Stanford University Medical Center Stanford California United States 94305-5216
    6 CCOP - Christiana Care Health Services Newark Delaware United States 19713
    7 MBCCOP - Howard University Cancer Center Washington District of Columbia United States 20060
    8 Veterans Affairs Medical Center - Gainesville Gainesville Florida United States 32608-1197
    9 Veterans Affairs Medical Center - Miami Miami Florida United States 33125
    10 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612-9497
    11 Veterans Affairs Medical Center - Tampa (Haley) Tampa Florida United States 33612
    12 Winship Cancer Institute of Emory University Atlanta Georgia United States 30322
    13 Veterans Affairs Medical Center - Atlanta (Decatur) Decatur Georgia United States 30033
    14 Veterans Affairs Medical Center - Lakeside Chicago Chicago Illinois United States 60611-4494
    15 Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois United States 60611
    16 CCOP - Central Illinois Decatur Illinois United States 62526
    17 Decatur Memorial Hospital Cancer Care Institute Decatur Illinois United States 62526
    18 CCOP - Evanston Evanston Illinois United States 60201
    19 CCOP - Illinois Oncology Research Association Peoria Illinois United States 61615-7828
    20 CCOP - Carle Cancer Center Urbana Illinois United States 61801
    21 Indiana University Cancer Center Indianapolis Indiana United States 46202-5289
    22 Veterans Affairs Medical Center - Indianapolis (Roudebush) Indianapolis Indiana United States 46202
    23 CCOP - Northern Indiana CR Consortium South Bend Indiana United States 46601
    24 CCOP - Cedar Rapids Oncology Project Cedar Rapids Iowa United States 52403-1206
    25 CCOP - Iowa Oncology Research Association Des Moines Iowa United States 50309-1016
    26 John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines Iowa United States 50309
    27 Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    28 John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines Iowa United States 50316-2301
    29 Burgess Health Center Onawa Iowa United States 51040
    30 CCOP - Wichita Wichita Kansas United States 67214-3882
    31 Veterans Affairs Medical Center - Wichita Wichita Kansas United States 67218
    32 MBCCOP - LSU Health Sciences Center New Orleans Louisiana United States 70112
    33 CCOP - Ochsner New Orleans Louisiana United States 70121
    34 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231
    35 Tufts - New England Medical Center Boston Massachusetts United States 02111
    36 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    37 CCOP - Michigan Cancer Research Consortium Ann Arbor Michigan United States 48106
    38 CCOP - Kalamazoo Kalamazoo Michigan United States 49007-3731
    39 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    40 CCOP - Duluth Duluth Minnesota United States 55805
    41 Veterans Affairs Medical Center - Minneapolis Minneapolis Minnesota United States 55417-2399
    42 University of Minnesota Cancer Center Minneapolis Minnesota United States 55455
    43 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
    44 CCOP - Metro-Minnesota Saint Louis Park Minnesota United States 55416
    45 Veterans Affairs Medical Center - Omaha Omaha Nebraska United States 68105
    46 CCOP - Missouri Valley Cancer Consortium Omaha Nebraska United States 68106
    47 Midlands Cancer Center at Midlands Community Hospital Papillion Nebraska United States 68128-4157
    48 CCOP - Southern Nevada Cancer Research Foundation Las Vegas Nevada United States 89106
    49 Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756-0002
    50 Veterans Affairs Medical Center - East Orange East Orange New Jersey United States 07018
    51 CCOP - Northern New Jersey Hackensack New Jersey United States 07601
    52 Cancer Institute of New Jersey at Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    53 MBCCOP - University of New Mexico HSC Albuquerque New Mexico United States 87131
    54 Albert Einstein Clinical Cancer Center Bronx New York United States 10461
    55 MBCCOP-Our Lady of Mercy Cancer Center Bronx New York United States 10466
    56 Veterans Affairs Medical Center - Brooklyn Brooklyn New York United States 11209
    57 Veterans Affairs Medical Center - New York New York New York United States 10010
    58 NYU School of Medicine's Kaplan Comprehensive Cancer Center New York New York United States 10016
    59 CCOP - Merit Care Hospital Fargo North Dakota United States 58122
    60 MetroHealth's Cancer Care Center at MetroHealth Medical Center Cleveland Ohio United States 44109
    61 Cleveland Clinic Taussig Cancer Center Cleveland Ohio United States 44195
    62 CCOP - Columbus Columbus Ohio United States 43206
    63 CCOP - Toledo Community Hospital Toledo Ohio United States 43623-3456
    64 CCOP - Oklahoma Tulsa Oklahoma United States 74136
    65 CCOP - Geisinger Clinic and Medical Center Danville Pennsylvania United States 17822-2001
    66 Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    67 Hahnemann University Hospital Philadelphia Pennsylvania United States 19102-1192
    68 Abramson Cancer Center of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
    69 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111-2497
    70 Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania United States 15236
    71 Veterans Affairs Medical Center - Pittsburgh Pittsburgh Pennsylvania United States 15240
    72 CCOP - MainLine Health Wynnewood Pennsylvania United States 19096
    73 CCOP - Sioux Community Cancer Consortium Sioux Falls South Dakota United States 57104
    74 Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus Nashville Tennessee United States 37212-2637
    75 Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center Nashville Tennessee United States 37232-6307
    76 CCOP - Scott and White Hospital Temple Texas United States 76508
    77 CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay Wisconsin United States 54307-3453
    78 Veterans Affairs Medical Center - Madison Madison Wisconsin United States 53705
    79 University of Wisconsin Comprehensive Cancer Center Madison Wisconsin United States 53792-0001
    80 CCOP - Marshfield Clinic Research Foundation Marshfield Wisconsin United States 54449
    81 Medical College of Wisconsin Cancer Center Milwaukee Wisconsin United States 53226-3596
    82 Veterans Affairs Medical Center - Milwaukee (Zablocki) Milwaukee Wisconsin United States 53295
    83 Westmead Breast Centre at NSW Breast Cancer Institute Westmead New South Wales Australia 2145
    84 Westmead Hospital Westmead New South Wales Australia 2145
    85 Instituto de Enfermedades Neoplasicas Lima Peru 34
    86 MBCCOP - San Juan San Juan Puerto Rico 00921-3201
    87 Veterans Affairs Medical Center - San Juan San Juan Puerto Rico 00927-5800
    88 San Juan City Hospital San Juan Puerto Rico 00936-7344
    89 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00054561
    Other Study ID Numbers:
    • CDR0000271174
    • ECOG-1301
    First Posted:
    Feb 6, 2003
    Last Update Posted:
    Jan 2, 2019
    Last Verified:
    Dec 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by , ,
    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
    Additional relevant MeSH terms:
    Head and Neck Neoplasms
    Vitamin E
    Interferons
    Interferon-alpha
    Isotretinoin

    Study Results

    No Results Posted as of Jan 2, 2019