Carotene and Retinol Efficacy Trial

Study Overview
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Brief Summary
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The Carotene and Retinol Efficacy Trial (CARET) was a randomized, double-blind, placebo-controlled trial of the cancer prevention efficacy and safety of a daily combination of 30 mg of beta-carotene and 25,000 IU of retinyl palmitate in 18,314 persons at high risk for lung cancer. CARET began in 1985, and the intervention was halted in January 1996, 21 months ahead of schedule, with the twin conclusions for definitive evidence of no benefit and substantial evidence of a harmful effect of the intervention on both lung cancer incidence and total mortality. CARET continued to follow and collect endpoints on their participants through 2005. During the active intervention phase of CARET, serum, plasma, whole blood, and lung tissue specimens were collected on participants. These biospecimens make up the CARET Biorepository. The CARET Biorepository is a valuable resource for population-based studies of the major human cancers. During CARET's twenty years of follow-up (1985-2005), we have received reports of 1,445 participants with lung cancer, 901 with prostate cancer, 433 with breast cancer, 334 with bladder cancer, 332 with colon cancer, and 1,429 with other cancers. CARET is one of the few trials that has prospectively collected serum, plasma, whole blood, blood spots (for DNA), and lung cancer tumor specimens, as well as smoking history and serial food frequency questionnaires (in some individuals for up to 12 years) in populations at high risk for lung cancer. This wealth of information in over 18,000 individuals makes the CARET Biorepository a special resource for cancer researchers.

Official Title
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Caret and Retinol Efficacy Trial: The Caret Coordinating Center

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Beta Carotene and Retinol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asbestos-exposed men who were: current smokers or quit within 15 years prior to enrollment had first exposure to asbestos on the job at least 15 years prior to enrollment had chest X-ray positive for changes compatible with asbestos exposure according to ILO criteria; or had been employed in a protocol-defined high-risk trade for at least 5 years, at least 10 years prior to enrollment. Heavy Smokers, men and women: cigarette smoking history of 20+ pack-years either current smokers or had quit within previous 6 years Exclusion Criteria: Pre-menopausal women History or cirrhosis or hepatitis within 12 months prior to enrollment Taking > 5500 IU daily vitamin A supplement Taking any beta-carotene supplement History of cancer within 5 years prior to enrollment SGOT > than 2.5X upper limit of normal, or alkaline phosphatase > 1.5X upper limit of normal taking less than 50% of study vitamins during the enrollment period between the First and Second Visits.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Asbestos-exposed participants and heavy smokers | Drug: Beta Carotene and Retinol<br>* Pilot participants (ppts): Asbestos-Exposed--15 mg/day beta-carotene + 25,000 IU/day retinol Heavy Smokers--30 mg/day beta-carotene + 25,000 IU/day retinol Vanguard & Efficacy ppts: Asbestos-exposed AND heavy smokers--30 mg/day beta-carotene + 25,000 IU/day retinol<br>|
| Placebo Comparator: 2<br>Asbestos-exposed participants and heavy smokers | Other: Placebo<br>* Two placebos, one each/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung Cancer Incidence |  | bi-annual | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other cancers |  | bi-annual |