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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Cocculine®
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>cocculine | Drug: Cocculine®<br>* 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.<br>|
| Placebo Comparator: 2<br>placebo | Drug: placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non metastatic breast cancer, Adjuvant chemotherapy, Nausea, Vomiting, Quality of life, Homeopathy