Beta-carotene and Alpha-tocopherol Chemoprevention of Second Primary Malignancies in Head and Neck Cancer Patients

March 12, 2018 updated by: Isabelle Bairati, Laval University

Epidemiologic studies suggest that low dietary intakes and low plasma concentrations of antioxidant vitamins and minerals are associated with increased risks of cancer, especially for epidermoid tumors. Patients with stage I or II head and neck cancer have a good prognosis, with a 5-year relative survival of 60% to 90%, depending of the tumor site. However, the benefit of treatment is often compromised by the occurrence of second primary cancers, which develop in 20% of patients during the first 5 years after diagnosis. We conducted a randomized chemoprevention trial among patients with head and neck cancer treated by radiation therapy to determine whether supplementation combining two antioxidants, alpha-tocopherol and beta-carotene, could reduce the incidence of second primary cancers in this patient population (primary objective of the trial). This study was conducted with funds from the NCIC (#008176,004738,013211) and was completed.

In this cohort of head and neck cancer patients, we evaluated whether nine potential prognostic serum markers measured at the time of diagnosis were related to recurrence, occurence of second primary cancers and survival. This study was conducted with funds from the NCIC (#018100) and was completed.

Presently, we evaluate genetic polymorphisms(GWAS) associated with prognosis (NCIC grant #019502). We also assess the relationship between vitamin D (dietary intake, serum level, and genetic polymorphisms of key vitamin D-related genes) and head and neck long-term outcomes (NCI grant #1R03CA141615-01).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

540

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Quebec City, Quebec, Canada, G1R 2J6
        • Laval University Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically documented stage I or II head and neck cancer

Exclusion Criteria:

  • Karnofsky performance score of less than 60
  • Multiple primary head and neck cancer
  • History of cancer
  • Severe cardiovascular disease
  • Inadequate renal, hepatic or hematologic function
  • Anticoagulant therapy
  • Pregnancy
  • Average daily supplement intake of beta-carotene or vitamin E in the preceding year greater than 6.0 mg and 50 IU, respectively.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Alpha-Tocopherol and Beta-Carotene
Patients received a daily supplementation of alpha-tocopherol (one capsule of 400 IU dl-alpha-tocopherol) and beta-carotene (one capsule of 30 mg) for 3 years after the end of radiation therapy. Due to ethical concerns, the beta-carotene supplementation was stopped during the trial (after the randomization of 156 patients). See details in JNCI, 2005: 97 (7), 481-8.
Dietary supplement: Alpha-Tocopherol and Beta-Carotene
Provided by Roche Vitamins Inc.
Placebo Comparator: Placebo
Patients received two capsules of placebos per day during 3 years. When the beta-carotene was stopped, they received only one capsule.
Dietary supplement: Placebo
Provided by Roche Vitamins Inc

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Second primary cancers
Time Frame: Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute and late side-effects of radiation therapy
Time Frame: During radiation therapy (RT), at the end of RT, one month after RT, six months after RT and 1 year after RT
During radiation therapy (RT), at the end of RT, one month after RT, six months after RT and 1 year after RT
Quality of life
Time Frame: Baseline, at the end of radiation therapy (RT), 1, 6,12,24 and 36 months after RT
Baseline, at the end of radiation therapy (RT), 1, 6,12,24 and 36 months after RT
Recurrence
Time Frame: Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Cancer free survival
Time Frame: Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Without recurrence and without second primary cancer
Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Overall survival
Time Frame: Every year
Every year
Disease free survival
Time Frame: Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Alive and without recurrence
Immediately and 1 month after radiation therapy, every 6 months during the 3 years following the end of radiation therapy, and then once a year until June 30, 2003
Survival until death from first cancer
Time Frame: every year
every year
Survival until death from second primary cancer
Time Frame: Every year
Every year
Survival until death from non-cancer causes
Time Frame: Every year
Every year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Laval University

Collaborators

National Cancer Institute (NCI)
Canadian Cancer Trials Group

Investigators

  • Principal Investigator: Isabelle Bairati, MD, PhD, Laval University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1994

Primary Completion (Actual)

June 1, 2003

Study Completion (Actual)

March 1, 2018

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Actual)

March 14, 2018

Last Update Submitted That Met QC Criteria

March 12, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27370
  • NCIC-4738 (Other Grant/Funding Number: National Cancer Institute of Canada)
  • NCIC-8176 (Other Grant/Funding Number: National Cancer Institute of Canada)
  • NCIC-13211 (Other Grant/Funding Number: National Cancer Institute of Canada)
  • NCIC-019502 (Other Grant/Funding Number: National Cancer Institute of Canada)
  • 1R03CA141615-01 (U.S. NIH Grant/Contract)
  • 018100 (Other Grant/Funding Number: National Cancer Institute of Canada)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

A letter was sent to each participant.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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