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

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 3

Conditions: Stage I-II Head and Neck Cancer

Treatments: Other: Placebo; Drug: 13-cis retinoic acid

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT03370367

C0590

Details and patient eligibility

About

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:

1. The time to diagnosis of second primary for the treatment versus control groups.
2. Survival time for the treatment versus control groups.
3. 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.

Enrollment: 189 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

  1. T1 NO
  2. T2 NO 3.142 Oropharynx
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  1. T1 NO

  2. T2 NO 3.143 Hypopharynx

  3. T1 NO 3.144 Larynx

  4. T1 NO

  5. 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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189 participants in 2 patient groups, including a placebo group

Arm A

Experimental group

Description:

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.

Treatment:

Drug: 13-cis retinoic acid

Arm B

Placebo Comparator group

Description:

Take 2 placebo pills once a day for up to 2 years.

Treatment:

Other: Placebo