Gemcitabine Combinations in Metastatic Breast Cancer (MBC), 1st Line

Study Overview
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Brief Summary
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The gemcitabine-paclitaxel and gemcitabine-platinum combinations have shown promise in the treatments of MBC; however, the optimal dosing schedules for these combinations have not yet been determined. The primary objective of this study is to compare the response rates of the gemcitabine-paclitaxel, gemcitabine-carboplatin, and gemcitabine-cisplatin combinations when administered on a biweekly schedule in metastatic breast cancer.

Official Title
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Randomized Phase II Study of Biweekly Gemcitabine-Paclitaxel, Biweekly Gemcitabine-Carboplatin and Biweekly Gemcitabine-Cisplatin as First-Line Treatment in Metastatic Breast Cancer After Anthracycline Failure

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: gemcitabine
* Drug: paclitaxel
* Drug: carboplatin
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with histological or cytological proven diagnosis of breast cancer Stage IV disease Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Scale Patients had to have previously received anthracycline based regimens as a adjuvant therapy or neo-adjuvant chemotherapy and then progressed and developed metastatic disease Adequate organ function Exclusion Criteria: Prior chemotherapy for metastatic disease Previous radiation therapy is allowed but must not have included whole pelvis radiation Known or suspected brain metastasis. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy and immunotherapy (including trastuzumab (Herceptin)) Peripheral neuropathy of Common Toxicity Criteria (CTC) Grade greater than 1. History of significant neurological or mental disorder, including seizures or dementia

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 |
| --- | --- |
| Experimental: Gemcitabine + Paclitaxel<br>gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. paclitaxel: 150 mg/m2, IV, every 14 days x 8 cycles. | Drug: gemcitabine<br>* 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles<br>* Other names: Gemzar;Drug: paclitaxel<br>* 150 mg/m2, IV, every 14 days x 8 cycles<br>|
| Experimental: Gemcitabine + Carboplatin<br>gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. carboplatin: Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles. | Drug: gemcitabine<br>* 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles<br>* Other names: Gemzar;Drug: carboplatin<br>* Area Under the Curve (AUC) 2.5, IV, every 14 days x 8 cycles<br>|
| Experimental: Gemcitabine + Cisplatin<br>gemcitabine: 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles. cisplatin: 50 mg/m2, IV, every 14 days x 8 cycles | Drug: gemcitabine<br>* 2500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles<br>* Other names: Gemzar;Drug: cisplatin<br>* 50 mg/m2, IV, every 14 days x 8 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. | baseline to measured progressive disease (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death or up to 24 months after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Time to Treatment Failure (TTTF) Event | TTTF event was defined as documented disease progression, death on study, start of non-protocol-specified anticancer therapy, or therapy discontinuation due to toxicity. TTTF for patients who were still participating in study without treatment failure at time of analysis were treated as censored at date of last tumor assessment. TTTF for patients who had discontinued from therapy for reasons other than toxicity and who did not experience treatment failure prior to therapy discontinuation were treated as censored on day of study discontinuation. | randomization to date of documented disease progression, death on study, start of non-protocol-specified anticancer therapy, or therapy discontinuation due to toxicity, whichever occurred first (up to 6 months) | 
| Progression Free Survival (PFS) | PFS was defined as the time from randomizaton to the date of documented disease progression or death on study, whichever occurred first. PFS for participants who discontinued from the study or who had not progressed at the time of analysis were treated as censored at the date of the last tumor assessment. | baseline to measured progressive disease or death (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death, or up to 24 months after randomization) | 
| Duration of Response | Duration of response was measured from time of first documentation of complete response (disappearance of all target lesions) or partial response (30% decrease in sum of longest diameter of target lesions), until date of PFS. Duration of response was censored on day of last tumor assessment for patients who had not progressed or who had discontinued study at time of analysis, and for cases where investigator determined patient had progressive disease and discontinued study therapy and/or started a new, non-protocol-specified anti-cancer therapy before documented disease progression. | time of response to progressive disease or death (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death, or up to 24 months after randomization) | 
| Overall Survival | Overall survival time is defined as the time from the date of randomization to date of death due to any cause. Survival time is censored at the date of last contact for patients who are still alive or lost to follow-up. | baseline to date of death from any cause (up to 34 months) |