Double Blind Phase III Trial of Effects of Low Dose 13-Cisretinoic Acid on Prevention of Second Primaries in Stages I-II Head and Neck Cancer

Study Overview
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Brief Summary
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In this trial the investigators propose to utilize 13-cRA to prevent dysplastic changes and second malignancies in patients with squamous cell carcinoma of the head and neck regions who have a high probability of cure from their primary cancer. Comparisons between patients treated by 13-cRA and patients receiving placebo will include: The time to diagnosis of second primary for the treatment versus control groups. Survival time for the treatment versus control groups. Secondarily, the cost-benefit ratio for 13-cRA will be analyzed by assessing the toxicities of 13-cis retinoic acid treated patients in comparison to those experienced by placebo treated patients.

Official Title
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Double Blind Phase III Trial of Effects of Low Dose 13-Cisretinoic Acid on Prevention of Second Primaries in Stages I-II Head and Neck Cancer

Conditions
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Stage I-II Head and Neck Cancer

Intervention / Treatment
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* Drug: 13-cis retinoic acid
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent i obtained, the approved form is signed, and on file at the institution. Histologically confirmed squamous cell carcinoma. All chest x-rays and cervical spine x-rays done after definitive treatment within 35 days prior to randomization and all hematology andchemistries done within 2 weeks prior to randomization. The following sites and stages of cancers will be eligible. Oral Cavity T1 NO T2 NO 3.142 Oropharynx T1 NO T2 NO 3.143 Hypopharynx 1. T1 NO 3.144 Larynx T1 NO T2 NO Age greater than 18 years. ECOG performance status 0 or 1. Patients must have adequate bone marrow, hepatic and renal function defined as follows: WBC >3,500/mm, Platelets > 125,000/mm.3 Total Bilirubin < 2 mg%, Serum creatinine < 2.5 mg%. Serum SGOT < 2x normal, Alkaline Phosphatase < 2x normal. Fasting Serum triglyceride levels < 210 mg %. Fasting cholesterol < 350 mg %. Patient may not be under systemic therapy for hyperlipidemia or have symptomatic arteriosclerotic coronary artery disease or have undergone coronary bypass surgery. The patient must have completed primary treatment of their cancer with surgery and/or radiation therapy within 730 days prior to randomization. The patient has had surgery and/or radiation therapy as outlined in Sections 5.0 and 6.0, and has been rendered disease-free. If currently receiving, patient must discontinue mega vitamin doses Exclusion Criteria: Women of child bearing potential. Patient with severe coronary artery disease (Class III-IV New York Heart Association.) Histology other than squamous cell carcinoma. Distant metastases. Completion of previous treatment for their primary cancer with radiation, or surgery (except for biopsy) more than 730 days ago. Prior, synchronous, or concurrent malignancy except basal cell skin cancer. Failure to be rendered disease-free of primary tumor (includes positive surgical margins). The patient has had prior therapy other than that outlined in Sections 5.0 and 6.0 of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>13-cis retinoic acid will be dispensed in 3.75 mg and 5 mg gelatin capsules. Take 2 capsules once a day for up to 2 years. | Drug: 13-cis retinoic acid<br>* Taken daily.<br>|
| Placebo Comparator: Arm B<br>Take 2 placebo pills once a day for up to 2 years. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to diagnosis of second primary for the treatment versus control groups. |  | 20 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time for the treatment versus control groups. |  | 20 years |