The treatment regimen consists of 28-day cycles of nab-paclitaxel 100 mg/m 2 on days 1, 8 and 15 and carboplatin AUC 6 on day 1 for four cycles followed by dose dense AC for four cycles. Bevacizumab is given at 10mg/kg every two weeks with chemotherapy for the first six cycles and is continued post-operatively to complete one year of treatment. Definitive surgical resection and radiation therapy are based on institutional standards.The study hypothesizes neoadjuvant weekly nab-paclitaxel plus carboplatin will demonstrate high pathologic complete remission (pCR) rates in TNBC patients due to the over-expression of the SPARC-protein in TNBC basal-like cancer with subsequent entrapment of albumin-bound nab-paclitaxel and DNA damage caused by carboplatin. Pathologic complete remission can be defined as the absence of invasive tumor cells in the breast specimen. The trial further hypothesizes that increased pCR rates will translate to improved disease-free survival (DFS) for the patients. II. ICE II: An investigational randomized phase II study on epirubicin (E) plus cyclophospamide (C) (or CMF) versus nab-paclitaxel plus capecitabine (PX) as adjuvant chemotherapy for elderly nonfrail patients with an increased risk for relapse of a primary carcinoma of the breast. (Abstract #TPS104) In this multicenter, controlled, open-label, randomized phase 2/3 study, 1,458 elderly patients (≥65) with an ECOG Performance Status and Charlson Scale of 0-2 and histologically confirmed unilateral or bilateral primary carcinoma of the breast with high risk disease classification, that have achieved complete resection of the tumor and ≥10 maxillary nodes will be treated. In addition, no evidence for distant metastasis could be seen in any patient. Patients will be randomized to receive either standard treatment (four cycles of either epirubicin plus cyclophospamideon (EC) day 1 q22 or six cycles intravenously; or cyclophosphamide/methotrexate/fluorouracil (CMF) on days 1 and 8 q29 intravenously – based on investigators’ decision) or six cycles of weekly nab-paclitaxel (100 mg/m 2) on days 1, 8, 15 q22 with a week of rest every six weeks in combination with capecitabine (2000 mg/m 2) days 1 to 14 orally, divided into two daily doses every three weeks for 6 cycles. The primary objective is to determine the safety and toxicity as well as the compliance of nab-paclitaxel plus capecitabine regimen. Main secondary objectives are disease free survival and overall survival with EC or CMF vs. nab-paclitaxel in combination with capecitabine. The initial, phase 2 study will examine the safety of nab-paclitaxel in combination with capecitabine compared to EC or CMF in the first 400 patients (200 per arm). A first interim safety analysis will be performed after 200 patients have gone through all cycles of chemotherapy. The phase 3 study will examine efficacy and safety for the entire planned cohort of 1,458 patients (n=729/arm). III. A multi-institutional double-blind phase II study evaluating response and surrogate biomarkers to carboplatin and nab-paclitaxel (CP) with or without vorinostat as preoperative systemic therapy (PST) in HER2-negative primary operable breast cancer (TBCRC008). (Abstract #TPS111) In this multi-institutional double-blind phase 2 study, women with unresected stage II-III HER2-negative breast cancer will be treated. The study includes both a run-in phase to investigate the safety of 12 weekly doses of carboplatin (AUC 2) and nab-paclitaxel (100mg/m 2) with vorinostat 400mg po daily (first 3 out of every 7 days) and a randomized phase 2 portion. The phase 2 treatment regimen consists of eligible women stratified by hormone receptor status and randomly assigned in a 1:1 ratio to nab-paclitaxel plus placebo or vorinostat, to include a sample size of 31 patients per arm. The primary endpoint is rate of pathologic complete response (pCR) with secondary endpoints including correlation of baseline and change in standardized uptake values on positron emission tomography with pCR and clinical CR, evaluation of safety and long term outcomes. Exploratory endpoints include comparison of pCR and clinical CR in women with triple-negative/basal-like features versus those without and evaluation of baseline and change in candidate gene methylation, gene expression and histone acetylation in tumor tissue. A sample size of 31 patients per arm will enable detection of a 25% pCR rate from a null response rate of 10% using a Simon two-stage design with 80% power and a 10% Type I error rate.
To date, six women have completed the run-in phase without dose-limiting toxicities and one woman has completed the phase 2 portion.About nab ® -Driven Chemotherapy Abraxis BioScience has developed a proprietary n anoparticle a lbumin- b ound ( nab) technology which leverages albumin nanoparticles for the active and targeted delivery of chemotherapeutics to the tumor. This nab-driven chemotherapy provides a new paradigm for penetrating the blood-stroma barrier to reach the tumor cell. The proposed mechanism of delivery of this nab-driven chemotherapy is thought to be by targeting a previously unrecognized tumor-activated, albumin-specific biologic pathway with a nanoshell of the human blood protein albumin. This nano-shuttle system is believed to activate an albumin-specific (Gp60) receptor-mediated transcytosis path through the cell wall of proliferating tumor cells, using caveolin-1 activated caveolar transport. Once in the stromal micro-environment, the albumin-bound drug may be preferentially localized by a second albumin-specific binding protein, SPARC, a protein secreted into the stroma by tumor cells. The resulting collapse of stroma surrounding the tumor cell may thus enhance the delivery of the nab-chemotherapeutic to the intracellular core of the tumor cell itself. About ABRAXANE ® ABRAXANE is the first clinical validation of the nanoparticle albumin bound ( nab) technology platform and is a treatment option for metastatic breast cancer. This protein-bound chemotherapy agent combines paclitaxel with albumin, a naturally-occurring human blood protein. ABRAXANE is currently in various stages of investigation for the treatment of the following cancers: expanded applications for metastatic breast, non-small cell lung, malignant melanoma, pancreatic and gastric. The U.S. Food and Drug Administration approved ABRAXANE for Injectable Suspension (paclitaxel protein albumin-bound particles for injectable suspension) (albumin-bound) in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. For the full prescribing information for ABRAXANE please visit http://www.abraxane.com. IMPORTANT SAFETY INFORMATION The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.
ABRAXANE can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE.Men should be advised to not father a child while receiving treatment with ABRAXANE. It is recommended that nursing be discontinued when receiving ABRAXANE therapy. ABRAXANE contains albumin (human), a derivative of human blood. Caution should be exercised when administering ABRAXANE concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4. ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm 3. It is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm 3 and platelets recover to a level >100,000 cells/mm 3 In the case of severe neutropenia (<500 cells/mm 3 for 7 days or more) during a course of ABRAXANE therapy, a dose reduction for subsequent courses is recommended. Sensory neuropathy occurs frequently with ABRAXANE. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE. Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients in the randomized trial. These events included chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary embolism, and hypertension. In the randomized metastatic breast cancer study, the most important adverse events included alopecia (90%), neutropenia (all cases 80%; severe 9%), sensory neuropathy (any symptoms 71%; severe 10%), asthenia (any 47%; severe 8%), myalgia/arthralgia (any 44%; severe 8%), anemia (all 33%; severe 1%), infections (24%), nausea (any 30%; severe 3%), vomiting (any 18%; severe 4%), diarrhea (any 27%; severe <1%), and mucositis (any 7%; severe <1%).
Other adverse reactions have included ocular/visual disturbances (any 13%; severe 1%), fluid retention (any 10%; severe 0%), hepatic dysfunction (elevations in bilirubin 7%, alkaline phosphatase 36%, AST [SGOT] 39%), renal dysfunction (any 11%; severe 1%), thrombocytopenia (any 2%; severe <1%), hypersensitivity reactions (any 4%; severe 0%), cardiovascular reactions (severe 3%), and injection site reactions (<1%). During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions have been reported with ABRAXANE.About Abraxis BioScience, Inc. Abraxis BioScience is a fully integrated global biotechnology company dedicated to the discovery, development and delivery of next-generation therapeutics and core technologies that offer patients safer and more effective treatments for cancer and other critical illnesses. The company's portfolio includes chemotherapeutic compound (ABRAXANE ®), which is based on the company's proprietary tumor targeting technology known as the nab ® platform. The first FDA approved product to use this nab ® platform, ABRAXANE, was launched in 2005 for the treatment of metastatic breast cancer and is now approved in 39 countries. The company continues to expand the nab ® platform through a robust clinical program and deep product pipeline. Abraxis trades on the NASDAQ Global Market under the symbol ABII. For more information about the company and its products, please visit http://www.abraxisbio.com. FORWARD-LOOKING STATEMENTS The statements contained in this press release that are not purely historical are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this press release include statements regarding our expectations, beliefs, hopes, goals, intentions, initiatives or strategies, including statements regarding the clinical development plan, and the timing and scope of clinical studies and trials, for ABRAXANE and the global commercialization of ABRAXANE. Because these forward-looking statements involve risks and uncertainties, there are important factors that could cause actual results to differ materially from those in the forward-looking statements. These factors include, without limitation, the fact that results from pre-clinical studies may not be predictive of results to be obtained in other pre-clinical studies or future clinical trials; delays in commencement and completion of clinical studies or trials, including slower than anticipated patient enrollment and adverse events occurring during the clinical trials; decisions by regulatory authorities regarding whether and when to approve ABRAXANE or product candidates for various indications as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of ABRAXANE and other products and product candidates; unexpected safety, efficacy or manufacturing issues with respect to ABRAXANE or product candidates; the need for additional data or clinical studies for ABRAXANE or product candidates; regulatory developments (domestic or foreign) involving the company's manufacturing facilities; the market adoption and demand of ABRAXANE and other products, the costs associated with the ongoing launch of ABRAXANE; research and development associated with the nab ® technology platform; the impact of pharmaceutical industry regulation; the impact of competitive products and pricing; the availability and pricing of ingredients used in the manufacture of pharmaceutical products; the ability to successfully manufacture products in a time-sensitive and cost effective manner; the acceptance and demand of new pharmaceutical products; and the impact of patents and other proprietary rights held by competitors and other third parties. Additional relevant information concerning risks can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2009 and in other documents it has filed with the Securities and Exchange Commission. The information contained in this press release is as of the date of this release. Abraxis assumes no obligations to update any forward-looking statements contained in this press release as the result of new information or future events or developments.
AVASTIN ® is a registered trademark of Roche.