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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00054561
First received: February 5, 2003
Last updated: February 6, 2009
Last verified: May 2004
  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 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 89 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Dong M. Shin, MD Winship Cancer Institute of Emory University
  More Information

Additional Information:
No publications provided

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

Keywords provided by National Cancer Institute (NCI):
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:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Vitamins
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Interferons
Interferon-alpha
Isotretinoin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Immunologic Factors
Dermatologic Agents

ClinicalTrials.gov processed this record on October 19, 2014