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

• Progression-free Survival [ Time Frame: Time from registration to progression or death (up to 5 years) ] [ Designated as safety issue: No ]
  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.
• Overall Survival [ Time Frame: Death or last follow-up (up to 5 years) ] [ Designated as safety issue: No ]
  Overall survival time was defined as the number of days from registration to the date of death or last follow-up
• Adverse Event [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]
  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

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.

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.

• Drug: Gemcitabine
  1000 mg/m2 (IV over 30 min) (days 1 and 8) on 21 day cycle
  Other Name: Gemzar
• Drug: Paclitaxel protein-bound particles for injectable suspension (albumin-bound)
  125 mg/m2 (IV over 30 min) (days 1 and 8) on 21 day cycle
  Other Name: nab (nanoparticle albumin-bound)-Paclitaxel, Abraxane

• Roy V, LaPlant BR, Gross GG, Bane CL, Palmieri FM; North Central Cancer Treatment Group. Phase II trial of weekly nab (nanoparticle albumin-bound)-paclitaxel (nab-paclitaxel) (Abraxane) in combination with gemcitabine in patients with metastatic breast cancer (N0531). Ann Oncol. 2009 Mar;20(3):449-53. Epub 2008 Dec 15.
• Roy V, LaPlant BR, Gross GG, et al.: NCCTG phase II trial N0531of weekly nab-paclitaxel (nab-p) in combination with gemcitabine (gem) in patients with metastatic breast cancer (MBC). [Abstract] J Clin Oncol 25 (Suppl 18): A-1048, 2007.
• Moreno-Aspitia A, Perez EA. North Central Cancer Treatment Group N0531: Phase II Trial of weekly albumin-bound paclitaxel (ABI-007; Abraxane) in combination with gemcitabine in patients with metastatic breast cancer. Clin Breast Cancer. 2005 Oct;6(4):361-4. No abstract available.

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