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

Phase 3
18 Years
Not Enrolling
Head and Neck Cancer

Thank you

Trial Information

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


- 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

- 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

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.

Inclusion Criteria


- 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

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Dong M. Shin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Winship Cancer Institute of Emory University


United States: Federal Government

Study ID:




Start Date:

August 2003

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms



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