Gemcitabine/ Trastuzumab and Gemcitabine/ Cisplatin/ Trastuzumab in Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study determines the proportion of metastatic breast cancer patients progression free after 6 months when treated with gemcitabine/ cisplatin/ trastuzumab or gemcitabine/ trastuzumab.

Detailed Description
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Rationale: Previous studies have demonstrated the anti-tumor efficacy of gemcitabine and trastuzumab against metastatic breast cancer when given alone and in combination. Yet, research indicates that the two drugs given together work more effectively than either alone. Laboratory studies testing the combination of trastuzumab and cisplatin have shown synergistic anti-tumor activity with the two drugs. In addition, clinical studies suggest a high level of anti-tumor activity with the combination of gemcitabine and cisplatin. Researchers are testing the triple drug combination of gemcitabine, trastuzumab, and cisplatin in the current study to evaluate the potential for enhanced responsiveness in patients with Her-2/neu overexpressing breast cancer as well as comparing it to the double drug combination of gemcitabine and trastuzumab. Purpose: This study will measure patient responses and compare the efficacy of a double drug combination (gemcitabine and trastuzumab) with a triple drug combination (gemcitabine, trastuzumab, and cisplatin) in patients with metastatic breast cancer. Side effects will be carefully assessed in patients. Treatment: Patients in this study will receive one of two treatment combinations. A computer will randomly assign patients to a treatment group. Group one will be given gemcitabine and trastuzumab. Gemcitabine will be given to patients on days 1 and 8, and trastuzumab on days 1, 8, and 15. Group two will receive gemcitabine, trastuzumab, and cisplatin. Gemcitabine and cisplatin will both be administered on days 1 and 8, and trastuzumab on days 1, 8, and 15. Each treatment cycle (for both groups) will last a total of 21 days. All study drugs will be administered through intravenous infusions. Several tests and exams will be given throughout the study to closely monitor patients. Thorough patient exams will be given at the beginning of each treatment cycle. Imaging tests will be done every two cycles for the first eight cycles and then every three cycles until study completion. Study treatment will be discontinued due to disease growth or unacceptable side effects.

Official Title
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A Randomized Phase II Study of Gemcitabine/ Trastuzumab and Gemcitabine/ Cisplatin/ Trastuzumab in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Trastuzumab
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Must have invasive metastatic breast cancer Tumor must be Her 2/neu 3+ by IHC (must be confirmed by Ohio State University pathology)or positive FISH Histological confirmation of invasive breast cancer either from the original diagnosis and/or diagnosis of metastatic disease. Tumor must be detectable clinically or radiographically (a positive bone scan is allowed as the only site of disease). Unidimensional measurements must be obtained whenever possible). Bone marrow only disease is not eligible for enrollment on this study. No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias, or evidence of prior myocardial infarction on EKG or ECHO. Patients must have normal LV function and LVEF(left ventricular ejection fraction)> 50% as demonstrated by either echo or muga within the proceeding 4 weeks. Must have adequate renal and hepatic function documented by a serum creatinine < 1.5 x the institutional upper limit of normal (ULN), serum bilirubin <1.5 x ULN and liver enzymes (AST, ALT, or alkaline phosphatase) < 2 x ULN (< 5 x ULN if hepatic metastasis) within 21 days prior to registration. Patients must have an ANC (absolute neutrophil count) > 1.5, platelets > 100,000, Hemoglobin >9.0 within 21 days of registration. If patients are on bisphosphonates at the time of registration, with a stable creatinine over the preceding 2 months, then they may continue bisphosphonates during the study. No more than one prior Trastuzumab/chemotherapy or Trastuzumab/biotherapy combination for metastatic disease. Additional Trastuzumab therapy may have been given in the adjuvant setting. Prior hormonal therapy is allowed for either adjuvant or metastatic disease. Must be >3 weeks since administration of last chemotherapy prior to initiation of treatment on this trial. Prior trastuzumab may have been administered within one week of initiation of treatment on this trial if the last dose was 2 mg/kg. Any prior trastuzumab dosing greater than 2 mg/kg requires a 3 week washout period. Patients may have received prior cisplatin or carboplatin for metastatic disease. No CNS(central nervous system)metastasis disease. No active infection at time of registration. Pregnant or nursing women may not participate in trial. Patients must be informed of the investigational nature of this study and sign and give written informed consent in accordance with institutional and federal guidelines. ECOG (Eastern Cooperative Oncology Group)performance status < 2 at the time of registration. Patients may participate in a non-treatment related protocol while participating in this study. No other active malignancy is allowed. Adequately treated basal cell, squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years is allowed.

Ages Eligible for Study
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Minimum Age: 18 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: Arm 1 Gemcitabine/Cisplatin/Trastuzumab<br>Gemcitabine 1000 mg/m2 iv over 30 minutes on days 1 and 8 Cisplatin 30 mg/m2 iv over 90 minutes on days 1 and 8 Trastuzumab 2 mg/kg iv over 30 minutes on days 1, 8 and 15 (if trastuzumab was not administered within the past 3 weeks, a loading dose of 4 mg/kg iv over 90 minutes will be given on the first day of cycle 1 only). | Drug: Gemcitabine<br>* 1000 mg/m2 IV over 30 minutes on Days 1 and 8.<br>* Other names: Gemzar;Drug: Trastuzumab<br>* 2 mg/kg IV on days 1, 8 and 15. If Trastuzumab has not been administered within the 3 weeks before starting this treatment, the first dose of Trastuzumab given on Cycle 1, Day 1 will be 4 mg/kg followed by 2 mg/kg weekly.<br>* Other names: Herceptin;Drug: Cisplatin<br>* 30 mg/m2 IV on Day 1 and Day 8.<br>* Other names: CDDP;|
| Active Comparator: Arm 2 Gemcitabine / Trastuzumab<br>Gemcitabine 1000 mg/m2 iv over 30 minutes on days 1 and 8 Trastuzumab 2 mg/kg iv over 30 minutes on days 1, 8 and 15 (if trastuzumab was not administered within the past 3 weeks, a loading dose of 4 mg/kg iv over 90 minutes will be given on the first day of cycle 1 only). | Drug: Gemcitabine<br>* 1000 mg/m2 IV over 30 minutes on Days 1 and 8.<br>* Other names: Gemzar;Drug: Trastuzumab<br>* 2 mg/kg IV on days 1, 8 and 15. If Trastuzumab has not been administered within the 3 weeks before starting this treatment, the first dose of Trastuzumab given on Cycle 1, Day 1 will be 4 mg/kg followed by 2 mg/kg weekly.<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Progression | Proportion of patients with metastatic breast cancer free of disease progression at 6 months following treatment | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Response Rate of Each Drug Combination | Response rate of the of the triple drug combination therapy and the double drug combination therapy regimens. | Up to 24 months | 
| Number of Participants With Grades 3 and Grade 4 Toxicity Profiles of the Drug Combinations | Adverse Events will be graded in accordance with the CTCAE Version 3.0 Toxicity grading criteria | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic