Carboplatin and Gemcitabine in Treating Patients With Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving carboplatin together with gemcitabine works in treating patients with locally advanced or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the overall response rate in patients with anthracycline- and taxane-resistant locally advanced or metastatic breast cancer treated with dose-dense carboplatin and gemcitabine hydrochloride. Secondary Determine the overall toxicity of this regimen in these patients. Determine the overall survival of patients treated with this regimen. Determine the time to disease progression in patients treated with this regimen. Determine the duration of response in patients treated with this regimen. Determine the time to treatment failure in patients treated with this regimen. OUTLINE: This is a nonrandomized, open-label study. Patients receive carboplatin IV over 30 minutes on day 1 and gemcitabine hydrochloride IV over 150 minutes on day 2. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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A Phase II Study of Carboplatin in Combination With Gemcitabine as a Dose Dense Schedule in Patients With Locally Advanced or Metastatic Breast Cancer That Are Resistant to Anthracyclines & Taxanes

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Gemcitabine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: DISEASE CHARACTERISTICS: histologically confirmed breast cancer, locally advanced or metastatic disease, recurrent or refractory disease, histological or cytological confirmation required for recurrence in a solitary site Must have received prior anthracycline and taxane as neoadjuvant, adjuvant, or metastatic therapy At least 1 measurable site of disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Palpable disease allowed, Lesions that have been irradiated in the advanced setting cannot be included as sites of measurable disease No nonmeasurable disease only, including the following: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Inflammatory breast disease Lymphangitic pulmonary disease Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions No HER2-positive disease, defined as 3+ by IHC OR positive by FISH or chromogenic in situ hybridization Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female, Menopausal status not specified, ECOG performance status 0-1, Estimated life expectancy ≥ 12 weeks, Not pregnant or nursing, fertile patients must use effective contraception during and for 3 months after completion of study therapy ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL ALT or AST < 2.5 times upper limit of normal (ULN) Bilirubin normal Alkaline phosphatase ≤ 2.5 times ULN Creatinine ≤ 1.25 times ULN OR creatinine clearance > 40 mL/min Calcium ≤ 1.2 times ULN No concurrent serious medical or psychiatric illness, including any serious active infection incompatible with the study No other primary malignancy except carcinoma in situ of the cervix, adequately treated nonmelanomatous skin cancer, or any other malignancy previously treated ≥ 5 years ago with no evidence of recurrence No peripheral neuropathy ≥ grade 2 PRIOR CONCURRENT THERAPY (See Disease Characteristics): Recovered from prior chemotherapy Prior hormonal therapy or immunotherapy allowed Antitumoral hormonal therapy must be discontinued prior to study entry More than 4 weeks since prior radiotherapy and recovered No prior radiotherapy to the whole pelvis or to ≥ 25% of the bone marrow No prior gemcitabine hydrochloride, cisplatin, or carboplatin No other cytotoxic chemotherapy for 21 days before and for 14 days after completion of study therapy More than 30 days since prior treatment with a drug (not including study drug) that has not received regulatory approval for any indication at the time of study entry Bisphosphonate therapy may not be initiated or discontinued within 4 weeks of study entry No more than 1 prior course of chemotherapy for metastatic disease Prior chemotherapy in the adjuvant setting allowed Concurrent palliative radiotherapy to existing painful lesions (soft tissue or bone) allowed New bone pain requiring radiotherapy > 4 weeks after first study treatment considered disease progression New pain in a soft tissue lesion without other objective changes may be irradiated provided ≥ 1 other site of nonirradiated measurable disease exists No other concurrent anticancer treatment No concurrent tamoxifen citrate, aromatase inhibitors, or progestagens

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
Intervention Model: Single Group Assignment
Interventional Model Description: In this non-randomized prospective trial, patients with human epidermal growth factor 2 (HER-2)-negative locally advanced or metastatic breast cancer that was anthracycline- and taxane-resistant were treated with carboplatin at a dose equivalent to an area under the concentration-time curve of 4.5 mg/ml.min on day 1 and gemcitabine 1500 mg/m2 on day 2 of every 2-week cycle. The primary end point was overall response rate.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with (HER-2)-negative and anthracycline- and taxane-resistant<br>Patients with human epidermal growth factor 2 (HER-2)-negative locally advanced or metastatic breast cancer that was anthracycline- and taxane-resistant | Drug: Carboplatin<br>* At a dose equivalent to an area under the concentration-time curve of 4.5 mg/ml.min on day 1 of every 2-week cycle<br>Drug: Gemcitabine Hydrochloride<br>* 1500 mg/m2 on day 2 of every 2-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (complete or partial response) | Assess the Overall response rate (complete or partial response) | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall toxicity as assessed by NCI CTCAE v3.0 | Summary Overall toxicity as assessed by NCI CTCAE v3.0 | 8 months | 
| Overall survival | Assess Overall survival | 8 months | 
| Time to disease progression | Assess Time to disease progression | 8 months | 
| Duration of response | Assess Duration of response | 8 months | 
| Time to treatment failure | Assess Time to treatment failure | 8 months | 

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