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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

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.

Intervention(s) in this Clinical Trial

• Drug: isotretinoin
• Drug: recombinant interferon alfa
• Drug: vitamin E
• Procedure: adjuvant therapy

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eastern Cooperative Oncology Group

Overall Clinical Trial Officials and Contacts

Dong M. Shin, MD Study Chair Emory University  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00054561

Study ID Number: CDR0000271174

ClinicalTrials.gov Identifier: NCT00054561

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database