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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00002586
First received: November 1, 1999
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Drug Toxicity
Lung Cancer
Drug: 13-cis retinoic acid
Dietary Supplement: Tocopherol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: ASSESSMENT OF INTERMEDIATE ENDPOINT BIOMARKERS TO 13-CIS RETINOIC ACID WITH OR WITHOUT ALPHA TOCOPHEROL OR OBSERVATION

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Treatment failure [ Time Frame: Three years ] [ Designated as safety issue: No ]
    Treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy


Enrollment: 96
Study Start Date: January 1993
Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 13-cis retinoic acid
13-cis retinoic acid 50 mg/d
Drug: 13-cis retinoic acid
Other Name: 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 Name: Isotretinoin, AccutaneT
Dietary Supplement: Tocopherol
Other Name: Vitamin E
No Intervention: Observation
Observation

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002586

Locations
United States, Colorado
Lung Cancer Institute
Denver, Colorado, United States, 80218
National Jewish Center for Immunology and Respiratory Medicine
Denver, Colorado, United States, 80206
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Denver, Colorado, United States, 80010
Veterans Affairs Medical Center - Denver
Denver, Colorado, United States, 80220
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: York E. Miller, MD University of Colorado, Denver
  More Information

Additional Information:
Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00002586     History of Changes
Other Study ID Numbers: 92-0382, NCI-V94-0506
Study First Received: November 1, 1999
Last Updated: May 5, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
non-small cell lung cancer
small cell lung cancer
drug/agent toxicity by tissue/organ

Additional relevant MeSH terms:
Lung Neoplasms
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Alpha-Tocopherol
Isotretinoin
Tocopherols
Tocotrienols
Tretinoin
Vitamin E
Vitamins
Antineoplastic Agents
Antioxidants
Dermatologic Agents
Growth Substances
Keratolytic Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014