Placebo-controlled Evaluation of Cocculine® Efficacy in the Management of Nausea After Chemotherapy in Breast Cancer.

Placebo-controlled Evaluation of Homeopathic Remedy (Cocculine®) Efficacy in the Management of Nausea After Adjuvant Chemotherapy in Non Metastatic Breast Cancer.

The purpose of the study is to determine whether a homeopathic remedy (Cocculine®) is effective in the prevention of chemotherapy-induced nausea in non metastatic breast cancer.

Eligible patients will be randomly assigned to one of 2-arms: Cocculine® or placebo.

The number of patients required to demonstrate a 0.5-point reduction in nausea on a visual analogue scale, assuming an alpha risk of 5% in a two-sided test and 85% power, is 396 (198 per arm). It has been estimated that the enrollment period should be 18 months.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Cocculine®; Drug: placebo

Detailed Description

The proportion of women with breast cancer treated by chemotherapy (CT) is increasing. CT-induced nausea and vomiting negatively impact patient quality of life.

The primary objective of the trial is to evaluate against a placebo the efficacy of Cocculine® administered as an adjunct to conventional treatments (corticosteroids and 5-HT3 receptor antagonists) for the management of nausea induced by a 1st course of adjuvant CT with FAC50, FEC100 or TAC in patients with non-metastatic breast cancer.

Secondary objectives are to test:

• the persistence of Cocculine® efficacy over the 2nd and 3rd CT courses
• the contribution of Cocculine® to the global management of nausea and vomiting during adjuvant CT
• patient compliance with Cocculine® dose.

Eligible patients will be randomly assigned to one of 2 arms: Cocculine® or placebo.

• Study Type: Interventional
• Enrollment (Actual): 431
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69000
    • Centre Léon Bérard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women with histologically proven non metastatic breast cancer
• No previous chemotherapy
• Treatment planning including 6 adjuvant CT courses with the first 3 being necessarily of the FAC50, FEC100 or TAC type
• Age>= 18 years
• ECOG performance status (PS) <= 2 (WHO scale)
• Patient able to read and understand French
• Written, voluntary, informed consent

Exclusion Criteria:

• Previous treatment with chemotherapy (including neo-adjuvant chemotherapy for breast cancer)
• Previous malignancies (except basal cell skin cancer or cervical cancer in situ or any other curatively treated malignancy in complete remission for more than 5 years)
• Contraindication to corticosteroids or 5-HT3 receptor antagonists
• Treatment with Cocculine® or any other anti-emetic drug in the 15 days before inclusion
• Pregnant or lactating women
• Follow-up impossible for social, geographical, familial or psychological reasons
• Patients who cannot be contacted by phone

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; placebo	Drug: placebo; 12 tablets in 3 days at each of the CT courses: 2 on the day before evening of the CT courses; 2 on the morning, noon and evening of the CT courses; 2 on morning and noon of the day after the CT courses.
Experimental: 1; cocculine	Drug: Cocculine®; 12 tablets in 3 days at each of the CT courses: 2 on the day before evening of the CT courses; 2 on the morning, noon and evening of the CT courses; 2 on morning and noon of the day after the CT courses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Score of "nausea" calculated using the FLIE questionnaire (Functional Living index for Emesis with 5-day recall)at the time of the 1rst adjuvant CT course	The nausea items of FLIE questionnaire are completed by patients on the 6th day of the 1st course.

Secondary Outcome Measures

Outcome Measure	Time Frame
Score of "vomiting" and global score of "nausea + vomiting" calculated using the FLIE questionnaire at the time of the 1st, 2nd and 3rd adjuvant CT courses	Nausea and vomiting items of FLIE questionnaire are completed by patients on the 6th day of the 1st, 2nd and 3rd adjuvant CT courses
Score of "nausea" calculated using the FLIE questionnaire at the time of the 2nd and 3rd adjuvant CT courses	Nausea items of FLIE questionnaire are completed by patients on the 6th day of the 2nd and 3rd adjuvant CT courses
Patient autoevaluation (D1-D5) of nausea severity using a visual analogue scale and of the frequency of vomiting during the 1st, 2nd and 3rd adjuvant CT courses	Visual analogue scale are completed by patients the 1st five days of the 1st, 2nd and 3rd adjuvant CT courses
Rate of toxic effects (nausea and vomiting) recorded by investigators at the end of each of the 6 CT courses	Recorded by investigators at the end of each of the 6 CT courses
Evaluation of compliance: patient autoevaluation and counting of remaining tablets	Patients register date and hour of tablets taking on a diary. Box remaining tablets will be count at the end of the 6 CT courses.

Collaborators and Investigators

• Sponsor: Centre Leon Berard
• Collaborators: BOIRON
• Investigators: Principal Investigator: RAY-COQUARD Isabelle, MD, Centre Leon Berard, France

Publications and helpful links

General Publications

• Pommier P, Gomez F, Sunyach MP, D'Hombres A, Carrie C, Montbarbon X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004 Apr 15;22(8):1447-53. doi: 10.1200/JCO.2004.07.063.
• Perol D, Provencal J, Hardy-Bessard AC, Coeffic D, Jacquin JP, Agostini C, Bachelot T, Guastalla JP, Pivot X, Martin JP, Bajard A, Ray-Coquard I. Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial. BMC Cancer. 2012 Dec 17;12:603. doi: 10.1186/1471-2407-12-603.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: December 7, 2006
• First Submitted That Met QC Criteria: December 7, 2006
• First Posted (Estimate): December 8, 2006

Study Record Updates

• Last Update Posted (Estimate): February 5, 2010
• Last Update Submitted That Met QC Criteria: February 4, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Quality of life; Non metastatic breast cancer; Adjuvant chemotherapy; Nausea; Vomiting; Homeopathy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Breast Diseases; Breast Neoplasms; Nausea; Antirheumatic Agents; Sinomenine
• Other Study ID Numbers: COCCULINE; ET2005-028

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No