ABI-007 (Nab-Paclitaxel) and Gemcitabine in Treating Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as ABI-007(Nab-Paclitaxel((Nanoparticle Albumin Bound)-Paclitaxel)) 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 ABI-007 together with gemcitabine works in treating women with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity of ABI-007 and gemcitabine, in terms of response rate in women with metastatic breast cancer. Determine the toxicity profile of this regimen, in terms of incidence and severity of observed toxic effects, in these patients. Secondary * Determine the time to disease progression and survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive ABI-007 IV over 30 minutes and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for up to 5 years. PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study within 20 months.

Official Title
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Phase II Trial of Weekly Nab (Nanoparticle Albumin Bound)-Paclitaxel (Nab-paclitaxel) (Abraxane®) in Combination With Gemcitabine in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Paclitaxel protein-bound particles for injectable suspension (albumin-bound)


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed invasive breast cancer - Clinical evidence of metastatic disease + No bone metastases or other non-measurable disease as the only evidence of metastasis Measurable disease, defined as at least 1 measurable lesion - The following are considered non-measurable disease: Small lesions (< 2 cm) Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusions Inflammatory breast disease Lymphangitis cutis or pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions HER2(human epidermal growth factor receptor 2)-positive disease allowed provided patient has received prior treatment with trastuzumab No evidence of active brain metastasis, including leptomeningeal involvement Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status ECOG 0-1 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Hepatic AST and ALT ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after completion of study treatment No pre-existing peripheral neuropathy > grade 1 No other clinically significant illness or significant medical condition that would preclude study participation No history of allergy or hypersensitivity to paclitaxel protein-bound particles in an injectable suspension, paclitaxel, gemcitabine, albumin, drug product excipients, or agents that are chemically similar to study drugs No serious medical risk factors involving any of the major organ systems that would preclude study participation No active stage III or IV invasive non-breast malignancy within the past 5 years PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy No more than 1 prior adjuvant chemotherapy regimen No prior chemotherapy for metastatic disease At least 6 months since prior adjuvant or neoadjuvant taxane More than 2 weeks since prior cytotoxic chemotherapy Prior neoadjuvant chemotherapy allowed No other concurrent chemotherapy Endocrine therapy Prior hormonal treatment as adjuvant therapy or for metastatic disease allowed Radiotherapy Prior radiotherapy to target lesion allowed provided there is evidence of disease progression after completion of treatment More than 2 weeks since prior radiotherapy, except radiotherapy to a non-target lesion only or single-dose palliative radiotherapy No concurrent radiotherapy Surgery Not specified Other More than 2 weeks since prior investigational drugs No concurrent participation in another clinical trial that is studying investigational procedures or therapies Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed for palliation of pain or lytic lesions from breast cancer

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nab-paclitaxel/Gemcitabine<br> | Drug: Gemcitabine<br>* 1000 mg/m2 (IV over 30 min) (days 1 and 8) on 21 day cycle<br>* Other names: Gemzar;Drug: Paclitaxel protein-bound particles for injectable suspension (albumin-bound)<br>* 125 mg/m2 (IV over 30 min) (days 1 and 8) on 21 day cycle<br>* Other names: nab (nanoparticle albumin-bound)-Paclitaxel, Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Confirmed Responses | Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. | Two consecutive evaluations at least 6 weeks apart | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation. | Time from registration to progression or death (up to 5 years) | 
| Overall Survival | Overall survival time was defined as the number of days from registration to the date of death or last follow-up | Death or last follow-up (up to 5 years) | 
| Adverse Event | Number of patients that experienced adverse events (grade 3 or more occurring in >5% of patients) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0 | Every 6 weeks | 

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