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

Sponsor

University of Colorado, Denver (Other)

Overall Status

Completed

CT.gov ID

NCT00002586

Collaborator

(none)

Enrollment

Locations

Arms

155

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Drug Toxicity Lung Cancer	Drug: 13-cis retinoic acid Dietary Supplement: Tocopherol	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jan 1, 1993

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Dec 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
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
No Intervention: Observation Observation

Arm

Intervention/Treatment

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

No Intervention: Observation

Observation

Outcome Measures

Primary Outcome Measures

Treatment failure [Three years]
Treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Patients must have at least a 30 pack year smoking history.
Patients must be a current smoker or ex-smoker who have not smoked for at least 6 months more.
Patients must have peripheral granulocyte count of > 1500 and platelet count of > 150,000.
Patients must have adequate hepatic function with bilirubin < 1.5 mg % and SGPT < 4 times institutional upper limits of normal.
Patients must have adequate renal function with serum creatinine < 1.5 mg %.
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:

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.
Patients must have no serious intercurrent illness including insulin dependent diabetes mellitus or hypercholesterolemia (>239mg/dl) / hypertriglyceridemia (>149mg/dl).
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.
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
Chest x-ray must not show evidence of tumor.
Patients must not be taking vitamin A or E supplements
Patients must not be taking tetracycline or minocycline.
Patients who have had prior chemotherapy or radiation therapy.
Women who are pregnant are ineligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado	United States	80010
2	National Jewish Center for Immunology and Respiratory Medicine	Denver	Colorado	United States	80206
3	Lung Cancer Institute	Denver	Colorado	United States	80218
4	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220