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

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.

Study Overview

• Status: Completed
• Conditions: Stage I-II Head and Neck Cancer
• Intervention / Treatment: Other: Placebo; Drug: 13-cis retinoic acid

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

Description

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
  1. T1 NO
  2. T2 NO 3.143 Hypopharynx

  1. T1 NO 3.144 Larynx

  1. T1 NO
  2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; Taken daily.
Placebo Comparator: Arm B; Take 2 placebo pills once a day for up to 2 years.	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group

Publications and helpful links

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 1989
• Primary Completion (Actual): January 15, 1999
• Study Completion (Actual): April 14, 2015

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin; Isotretinoin
• Other Study ID Numbers: C0590

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes