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

NCT00169845 | Completed Phase 3 DMC

• 7 other identifiers: 27370NCIC-4738NCIC-8176NCIC-13211NCIC-0195021R03CA141615-01018100
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Neoplasms

Keywords

chemoprevention trial; antioxidant; alpha-tocopherol; beta-carotene; second primary cancer; head and neck cancer; adverse effect of radiation therapy; quality of life; mortality; cancer free survival; cancer recurrence

Outcome Measures

Primary Outcomes (1)

• Second primary cancers

  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 Outcomes (9)

• Acute and late side-effects of radiation therapy

  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

  Baseline, at the end of radiation therapy (RT), 1, 6,12,24 and 36 months after RT

• 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

• Cancer free survival

  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

  Every year

Study Arms (2)

Alpha-Tocopherol and Beta-Carotene

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Alpha-Tocopherol and Beta-Carotene DIETARY_SUPPLEMENT

Provided by Roche Vitamins Inc.

Alpha-Tocopherol and Beta-Carotene

Placebo DIETARY_SUPPLEMENT

Provided by Roche Vitamins Inc

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented stage I or II head and neck cancer

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laval University: lead
• Canadian Cancer Trials Group: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Laval University Cancer Research Center

Québec, Quebec, G1R 2J6, Canada

Location

Related Publications (16)

• Bairati I, Meyer F, Gelinas M, Fortin A, Nabid A, Brochet F, Mercier JP, Tetu B, Harel F, Abdous B, Vigneault E, Vass S, Del Vecchio P, Roy J. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol. 2005 Aug 20;23(24):5805-13. doi: 10.1200/JCO.2005.05.514. Epub 2005 Jul 18.

  PMID: 16027437 RESULT

• Bairati I, Meyer F, Gelinas M, Fortin A, Nabid A, Brochet F, Mercier JP, Tetu B, Harel F, Masse B, Vigneault E, Vass S, del Vecchio P, Roy J. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005 Apr 6;97(7):481-8. doi: 10.1093/jnci/dji095.

  PMID: 15812073 RESULT

• Bairati I, Meyer F, Jobin E, Gelinas M, Fortin A, Nabid A, Brochet F, Tetu B. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer. 2006 Nov 1;119(9):2221-4. doi: 10.1002/ijc.22042.

  PMID: 16841333 RESULT

• Meyer F, Bairati I, Jobin E, Gelinas M, Fortin A, Nabid A, Tetu B. Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients. Nutr Cancer. 2007;59(1):29-35. doi: 10.1080/01635580701397590.

  PMID: 17927499 RESULT

• Sackett MK, Bairati I, Meyer F, Jobin E, Lussier S, Fortin A, Gelinas M, Nabid A, Brochet F, Tetu B. Prognostic significance of cyclooxygenase-2 overexpression in glottic cancer. Clin Cancer Res. 2008 Jan 1;14(1):67-73. doi: 10.1158/1078-0432.CCR-07-2028.

  PMID: 18172254 RESULT

• Meyer F, Fortin A, Gelinas M, Nabid A, Brochet F, Tetu B, Bairati I. Health-related quality of life as a survival predictor for patients with localized head and neck cancer treated with radiation therapy. J Clin Oncol. 2009 Jun 20;27(18):2970-6. doi: 10.1200/JCO.2008.20.0295. Epub 2009 May 18.

  PMID: 19451440 RESULT

• Meyer F, Samson E, Douville P, Duchesne T, Liu G, Bairati I. Serum prognostic markers in head and neck cancer. Clin Cancer Res. 2010 Feb 1;16(3):1008-15. doi: 10.1158/1078-0432.CCR-09-2014. Epub 2010 Jan 26.

  PMID: 20103685 RESULT

• Nourissat A, Bairati I, Samson E, Fortin A, Gelinas M, Nabid A, Brochet F, Tetu B, Meyer F. Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer. Cancer. 2010 May 1;116(9):2275-83. doi: 10.1002/cncr.25041.

  PMID: 20187097 RESULT

• Meyer F, Liu G, Douville P, Samson E, Xu W, Adjei A, Bairati I. Dietary vitamin D intake and serum 25-hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients. Int J Cancer. 2011 Apr 1;128(7):1741-6. doi: 10.1002/ijc.25496. Epub 2010 Jun 7.

  PMID: 20533282 RESULT

• Meyer F, Bairati I, Fortin A, Gelinas M, Nabid A, Brochet F, Tetu B. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: a randomized trial among head and neck cancer patients. Int J Cancer. 2008 Apr 1;122(7):1679-83. doi: 10.1002/ijc.23200.

  PMID: 18059031 RESULT

• Nourissat A, Bairati I, Fortin A, Gelinas M, Nabid A, Brochet F, Tetu B, Meyer F. Factors associated with weight loss during radiotherapy in patients with stage I or II head and neck cancer. Support Care Cancer. 2012 Mar;20(3):591-9. doi: 10.1007/s00520-011-1132-x. Epub 2011 Mar 20.

  PMID: 21424341 RESULT

• Meyer F, Fortin A, Wang CS, Liu G, Bairati I. Predictors of severe acute and late toxicities in patients with localized head-and-neck cancer treated with radiation therapy. Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1454-62. doi: 10.1016/j.ijrobp.2011.04.022. Epub 2011 Jun 2.

  PMID: 21640495 RESULT

• Azad AK, Bairati I, Samson E, Cheng D, Cheng L, Mirshams M, Savas S, Waldron J, Wang C, Goldstein D, Xu W, Meyer F, Liu G. Genetic sequence variants and the development of secondary primary cancers in patients with head and neck cancers. Cancer. 2012 Mar 15;118(6):1554-65. doi: 10.1002/cncr.26446. Epub 2011 Aug 25.

  PMID: 22009713 RESULT

• Azad AK, Bairati I, Samson E, Cheng D, Mirshams M, Qiu X, Savas S, Waldron J, Wang C, Goldstein D, Xu W, Meyer F, Liu G. Validation of genetic sequence variants as prognostic factors in early-stage head and neck squamous cell cancer survival. Clin Cancer Res. 2012 Jan 1;18(1):196-206. doi: 10.1158/1078-0432.CCR-11-1759. Epub 2011 Nov 10.

  PMID: 22076708 RESULT

• Azad AK, Bairati I, Qiu X, Huang H, Cheng D, Liu G, Meyer F, Adjei A, Xu W. Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients. Int J Cancer. 2013 Jun 1;132(11):2520-7. doi: 10.1002/ijc.27946. Epub 2012 Dec 14.

  PMID: 23169318 RESULT

• Azad AK, Bairati I, Qiu X, Girgis H, Cheng L, Waggott D, Cheng D, Mirshams M, Ho J, Fortin A, Vigneault E, Huang SH, O'Sullivan B, Waldron J, Boutros PC, Goldstein D, Meyer F, Xu W, Liu G. A genome-wide association study of non-HPV-related head and neck squamous cell carcinoma identifies prognostic genetic sequence variants in the MAP-kinase and hormone pathways. Cancer Epidemiol. 2016 Jun;42:173-80. doi: 10.1016/j.canep.2016.05.001. Epub 2016 May 9.

  PMID: 27173062 RESULT

MeSH Terms

Conditions

Neoplasms; Neoplasms, Second Primary; Head and Neck Neoplasms; Radiation Injuries

Interventions

alpha-Tocopherol; beta Carotene

Condition Hierarchy (Ancestors)

Neoplasms by Site; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Tocopherols; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Isabelle Bairati, MD, PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor (MD, PhD)

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 15, 2005
• Study Start: October 1, 1994
• Primary Completion: June 1, 2003
• Study Completion: March 1, 2018
• Last Updated: March 14, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)