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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00054561
Recruitment Status : Completed
First Posted : February 6, 2003
Last Update Posted : January 2, 2019
National Cancer Institute (NCI)
Information provided by:
Eastern Cooperative Oncology Group

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
Head and Neck Cancer Biological: recombinant interferon alfa Dietary Supplement: vitamin E Drug: isotretinoin Procedure: adjuvant therapy Phase 3

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
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 : August 2003
Actual Primary Completion Date : December 2004
Actual Study Completion Date : May 1, 2009

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified


  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3


  • 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


  • Creatinine no greater than 1.2 mg/dL


  • 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


Biologic therapy

  • Not specified


  • 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


  • See Disease Characteristics
  • Recovered from prior radiotherapy


  • See Disease Characteristics
  • Recovered from prior surgery


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00054561

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Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
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Study Chair: Dong M. Shin, MD Emory University

Layout table for additonal information Identifier: NCT00054561    
Other Study ID Numbers: CDR0000271174
First Posted: February 6, 2003    Key Record Dates
Last Update Posted: January 2, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eastern Cooperative Oncology Group:
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:
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Head and Neck Neoplasms
Neoplasms by Site
Vitamin E
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Dermatologic Agents