Docetaxel and Cisplatin Chemotherapy With or Without High Dose Proton Pump Inhibitor in Metastatic Breast Cancer

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the efficacy and tolerability of high dose proton pump inhibitor combined with chemotherapy in metastatic breast cancer.

Detailed Description
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High dose proton pump inhibitor (PPI) has been proved beneficial and it improved efficacy when combined with chemotherapy in preclinical and clinical trials.This study was designed to explore whether adding a proton pump inhibitor into docetaxel and cisplatin chemotherapy improves efficacy and does not affect tolerability in metastatic breast cancer.

Official Title
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Phase II Study of Docetaxel and Cisplatin Chemotherapy Versus Docetaxel and Cisplatin Chemotherapy Combined With High Dose Proton Pump Inhibitor in Metastatic Breast Cancer

Conditions
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Breast Cancer, Metastasis, Neoplasm

Intervention / Treatment
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* Drug: Arm C
* Drug: Arm B
* Drug: Arm A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Female, ≥ 18 years. Histologically confirmed invasive breast cancer. Metastatic breast cancer. Karnofsky Performance Status ≥60. Life expectancy of more than 3 months. Subject must have adequate organ function. Normal laboratory values: hemoglobin > 80g/dl, neutrophils > 2.0×10^9/L, platelets > 80×10^9/L, serum creatinine < upper limit of normal (ULN), serum bilirubin < ULN, ALT and AST < 2.5×ULN, AKP < 5×ULN. Negative serum pregnancy test for women with childbearing potential. Good conditions for infusion and willing to have phlebotomy throughout whole study. Have ceased anti-tumor treatments including endocrinotherapy and bio-targeted therapy for more than 28 days. Have at least one target lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. No prior use of docetaxel or has used docetaxel in adjuvant/neo-adjuvant chemotherapy and has a relapse free survival of at least 12 months. Exclusion Criteria: Pregnant or lactating females. History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety. Active or uncontrolled infection. Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure. Concomitant with brain metastases. Have received chemotherapy after metastasis.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: arm A<br>docetaxel and cisplatin chemotherapy | Drug: Arm A<br>* Docetaxel and cisplatin chemotherapy. Docetaxel 75mg/m2 intravenous d1, cisplatin 75mg/m2 intravenous d1,repeated every 3 weeks.Each patient is designed to receive no more than 6 cycles of chemotherapy.<br>* Other names: Cisplatin;|
| Experimental: arm B<br>docetaxel and cisplatin chemotherapy combined with PPI 160mg per day. | Drug: Arm B<br>* Docetaxel and cisplatin chemotherapy combined with lower dose PPI. Docetaxel 75mg/m2 intravenous d1, cisplatin 75mg/m2 intravenous d1,repeated every 3 weeks.Each patient is designed to receive no more than 6 cycles of chemotherapy.PPI 160mg p.o. d1-3 every week for 66 weeks.<br>* Other names: esomeprazole;|
| Experimental: arm C<br>docetaxel and cisplatin chemotherapy combined with PPI 200mg per day. | Drug: Arm C<br>* Docetaxel and cisplatin chemotherapy combined with high dose PPI. Docetaxel 75mg/m2 intravenous d1, cisplatin 75mg/m2 intravenous d1,repeated every 3 weeks.Each patient is designed to receive no more than 6 cycles of chemotherapy.PPI 200mg p.o. d1-3 every week for 66 weeks.<br>* Other names: esomeprazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure,Objective response,Overall survival,Safety |  | six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastasis Breast Cancer, Proton Pump Inhibitor, Chemotherapy, Phase II study, TTP