Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI ECOG-1301 E1301, NCT00054561

Special Category: CTSU trial

Objectives

1. 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.
2. Determine the qualitative and quantitative toxicity of this regimen in these patients.
3. Compare the overall and disease-free survival of patients treated with this regimen vs those who undergo observation only.
4. Determine whether alterations of p53 gene, retinoic acid receptors, retinoid-regulated gene, and interferon-responsive genes are associated with clinical outcome in these patients.

Entry 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]

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

A total of 376 patients (188 per treatment arm) will be accrued for this study within 3.75 years.

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.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Dong Shin, MD, Protocol chair		Ph: 404-778-5990; 888-946-7447 Email: dong_shin@emoryhealthcare.org

Registry Information
Official Title		Phase III Randomized Study of Adjuvant Biologic Therapy in Patients with Stages III/IV Head and Neck Squamous Cell Carcinoma
Trial Start Date		2003-08-21
Registered in ClinicalTrials.gov		NCT00054561
Date Submitted to PDQ		2003-01-16
Information Last Verified		2004-05-07
NCI Grant/Contract Number		U10-CA21115

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