13-Cis Retinoic Acid With or Without Vitamin E for Prevention of Lung Cancer (13-Cis)

ASSESSMENT OF INTERMEDIATE ENDPOINT BIOMARKERS TO 13-CIS RETINOIC ACID WITH OR WITHOUT ALPHA TOCOPHEROL OR OBSERVATION

RATIONALE: 13 Cis retinoic acid may prevent the development of cancer cells.

PURPOSE: Randomized double-blinded phase II trial to study the effectiveness of 13-cis retinoic acid with or without vitamin E for chemoprevention or observation of cancer in persons at high risk of developing lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Drug Toxicity
• Intervention / Treatment: Drug: 13-cis retinoic acid; Dietary supplement: Tocopherol

Detailed Description

OBJECTIVES:

• To determine if alpha tocopherol can reduce the toxicities of low dose 13-cis retinoic acid administered for one year.
• To access the adequacy of the collected specimens for studies of intermediate endpoint markers.

• to establish a depository of biologic specimens for future studies of new biomarkers.

  • Arm 1: Patients receive oral 13-cis retinoic acid daily.
  • Arm 2: Patients receive oral 13-cis retinoic acid and oral vitamin E daily.
  • Arm 3: Patients undergo observation only. Treatment continues in arms I and II for 1 year in the absence of unacceptable toxicity.

Patients are followed annually for 2 years.

PROJECTED ACCRUAL: A total of 100 patients (33 Arm 1, 33 Arm 2, and 34 Arm 3) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
    • Denver, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80206
      • National Jewish Center for Immunology and Respiratory Medicine
    • Denver, Colorado, United States, 80218
      • Lung Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients identified through the Tissue Procurement/Screening Project with mild, moderate or severe dysplasia, Ca In situ OR surgically cured patients with head and neck cancer who are found to have mild atypia or greater on their staging bronchoscopy. (This includes carcinoma in situ). Also eligible are patients with Stage I and II non-small cell lung cancer who are disease free greater than 36 months.
2. Patients must have at least a 30 pack year smoking history.
3. Patients must be a current smoker or ex-smoker who have not smoked for at least 6 months more.
4. Patients must have peripheral granulocyte count of > 1500 and platelet count of > 150,000.
5. Patients must have adequate hepatic function with bilirubin < 1.5 mg % and SGPT < 4 times institutional upper limits of normal.
6. Patients must have adequate renal function with serum creatinine < 1.5 mg %.
7. All patients must be informed of the investigational nature of the study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

1. Patients must not have a current or past history of cancer within the past 5 years with the exception of surgically cured head and neck cancer or surgically cured Stage I or II lung cancer > 36 months from diagnosis or skin cancer or in situ cancers.
2. Patients must have no serious intercurrent illness including insulin dependent diabetes mellitus or hypercholesterolemia (>239mg/dl) / hypertriglyceridemia (>149mg/dl).
3. Patients must not have evidence of clinically active coronary artery disease including myocardial infarction within 6 weeks, chest pain or poorly controlled congestive heart failure or any other serious medical condition, which would preclude a patient from undergoing a bronchoscopy.
4. Patients must not have cardiac dysrhythmia that is potentially life threatening such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well controlled atrial fibrillation or rare (<2/minute) premature ventricular contractions are not exclusionary
5. Chest x-ray must not show evidence of tumor.
6. Patients must not be taking vitamin A or E supplements
7. Patients must not be taking tetracycline or minocycline.
8. Patients who have had prior chemotherapy or radiation therapy.
9. Women who are pregnant are ineligible

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation
Experimental: 13-cis retinoic acid; 13-cis retinoic acid 50 mg/d	Drug: 13-cis retinoic acid; Other Names: Isotretinoin, AccutaneT
Experimental: 13-Cis Retinoic Acid and Tocopherol; 13-Cis Retinoic Acid (50 mg/day) Tocopherol (800 mg/day)	Drug: 13-cis retinoic acid; Other Names: Isotretinoin, AccutaneT; Dietary supplement: Tocopherol; Other Names: Vitamin E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure	Treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy	Three years

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: York E. Miller, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Kelly K, Kittelson J, Franklin WA, Kennedy TC, Klein CE, Keith RL, Dempsey EC, Lewis M, Jackson MK, Hirsch FR, Bunn PA, Miller YE. A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer. Cancer Prev Res (Phila). 2009 May;2(5):440-9. doi: 10.1158/1940-6207.CAPR-08-0136. Epub 2009 Apr 28.

Study record dates

Study Major Dates

• Study Start: January 1, 1993
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; small cell lung cancer; drug/agent toxicity by tissue/organ
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Dermatologic Agents; Micronutrients; Vitamins; Keratolytic Agents; Antioxidants; Vitamin E; Tocopherols; alpha-Tocopherol; Tocotrienols; Tretinoin; Isotretinoin
• Other Study ID Numbers: 92-0382; NCI-V94-0506 (Other Grant/Funding Number: National Cancer Institute)