Carotene and Retinol Efficacy Trial (CARET)

Caret and Retinol Efficacy Trial: The Caret Coordinating Center

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Beta Carotene and Retinol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18314
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Asbestos-exposed participants and heavy smokers	Drug: Beta Carotene and Retinol; 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
Placebo Comparator: 2; Asbestos-exposed participants and heavy smokers	Other: Placebo; Two placebos, one each/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Lung Cancer Incidence	bi-annual

Secondary Outcome Measures

Outcome Measure	Time Frame
Other cancers	bi-annual

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Gary E Goodman, MD, Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 1985
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: July 8, 2008
• First Submitted That Met QC Criteria: July 9, 2008
• First Posted (Estimate): July 10, 2008

Study Record Updates

• Last Update Posted (Estimate): September 26, 2012
• Last Update Submitted That Met QC Criteria: September 25, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Provitamins; Beta Carotene; Carotenoids; Vitamin A
• Other Study ID Numbers: FHCRC IR-4239A; U01CA063673 (U.S. NIH Grant/Contract); 4239A (Other Identifier: FHCRC)