Docetaxel With or Without a Phytochemical in Treating Patients With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Dietary supplements, such as phytochemicals, may stop or delay the development of breast cancer. It is not yet known whether giving docetaxel together with a phytochemical is more effective than giving docetaxel alone in treating patients with breast cancer. PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with a phytochemical works compared with giving docetaxel alone as first- or second-line therapy in treating patients with breast cancer.

Detailed Description
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OBJECTIVES: Primary To compare the response rate in HER2-negative patients with locally advanced or metastatic breast cancer or locoregional breast cancer recurrence treated with docetaxel and a dietary phytochemical vs docetaxel alone. Secondary To compare the overall clinical benefit rate (i.e., objective response plus stable disease) in patients treated with these regimens. To compare time to progression in patients treated with these regimens. To compare overall survival of patients treated with these regimens. To assess biomarkers of response in blood samples from patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to recruitment center and line of chemotherapy (first vs second line of docetaxel). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive docetaxel as in arm I. Patients also receive an oral dietary phytochemical twice on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.

Official Title
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An Open-label, Randomised, Phase II Study of Docetaxel in Combination With a Dietary Phytonutrient in First or Second Line Treatment for Patients With HER2 Negative Locally Advanced or Metastatic Breast Cancer, or Loco-regional Recurrence Not Amenable to Treatment by Surgery or Radiotherapy.

Conditions
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Breast Cancer

Intervention / Treatment
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* Dietary Supplement: Curcumin
* Drug: Taxotere


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the breast, meeting 1 of the following criteria: Locally advanced disease Documented metastatic disease without overexpression of Her2/neu Must have received prior anthracycline-containing regimen as neoadjuvant, adjuvant, or first-line chemotherapy for metastatic breast cancer Loco-regional recurrence not amenable to treatment by surgery or radiotherapy At least one measurable lesion according to RECIST criteria No bone lesion only disease Must be a candidate for taxane-based chemotherapy HER2-negative disease No symptomatic brain metastases Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified WHO performance status 0-2 Life expectancy ≥ 3 months ANC ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL Serum creatinine < 140 µmol/L OR creatinine clearance > 60 mL/min Total bilirubin ≤ upper limit of normal (ULN) AST and ALT ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No history of significant neurologic (i.e., peripheral neuropathy ≥ grade 2) or psychiatric disorders, including psychotic disorders, dementia, or seizures that would prohibit the understanding, observance, and giving of informed consent No other prior or concomitant malignancies except adequately treated carcinoma in situ of the cervix uteri, basal cell or squamous cell carcinoma of the skin, or other cancer curatively treated with surgery and/or radiotherapy No concurrent severe and/or uncontrolled co-morbid medical condition No medically unstable patients No uncontrolled infection No autoimmune disease and/or chronic active inflammation No psychological, familial, social, or geographical reasons that would make clinical follow-up impossible No malabsorption syndrome or disease significantly affecting gastrointestinal function No dysphagia ≥ grade 2 No history of hypersensitivity to taxanes or known excipients, including polysorbate 80 PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior major resection of the stomach or proximal small bowel Prior hormonal therapy as adjuvant treatment and/or treatment of metastatic disease allowed provided that the patient has progressive disease at study entry Hormonal treatment must be discontinued prior to study entry No more than 1 prior chemotherapy regimen for metastatic disease More than 30 days since prior investigational drug More than 3 weeks since prior NSAIDs or COX_2 inhibitors No other concurrent anticancer therapy No other concurrent dietary phytonutrients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curcumine<br>With curcumin capsules | Dietary Supplement: Curcumin<br> <br> Drug: Taxotere<br> <br> |
| Active Comparator: Drug taxotere only<br>Without curcumin | Drug: Taxotere<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as assessed by RECIST criteria |  | From the date of randomization until the end of the treatment, assessed up to 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall clinical benefit rate as assessed by RECIST criteria |  | From the date of randomization until the end of the treatment, assessed up to 21 weeks | 
| Time to progression as assessed by RECIST criteria |  | From date of randomization until the date of first documented progression or date of death from any cause, assessed up to 21 weeks | 
| Overall survival as assessed by RECIST criteria | Evaluate overall survival (between inclusion and death whatever the cause) | From the date of randomization until the date of death from any cause | 
| Safety as assessed by NCI CTCAE v3.0 |  | From the date of randomization until the end of the treatment, assessed up to 21 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, recurrent breast cancer, stage IIIA breast cancer, HER2-negative breast cancer