Abraxis BioScience, Inc. has announced that data from a Phase I trial showing clinical benefit of ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin bound) in combination with Gemzar® (gemcitabine) in more than 70 percent of advanced pancreatic patients were presented at the American Association for Cancer Research (AACR) Annual Meeting held April 12-16, 2008 in San Diego, California.
“In this trial, we saw a high level of activity, including a rapid decrease in CA 19-9, a marker for pancreatic cancer, and a dramatic decrease in the sizes of tumors,” said Daniel Von Hoff, M.D., Physician in Chief of the Translational Genomic Research Institute (TGen) and Chief Medical Officer for the Scottsdale Clinical Research Institute at Scottsdale Healthcare in Arizona. “The fact that we saw this kind of activity in a Phase I trial is impressive, especially since Phase I trials are typically designed to test for safety.”
In an ongoing research program, SPARC (Secreted Protein Acidic and Rich in Cysteine) was commonly found in pancreatic cancer specimens; a finding that was the basis for this Phase I clinical trial. SPARC is also believed to be a target for nab-paclitaxel due to a SPARC-albumin interaction. Patients whose tumors are SPARC positive have been previously associated with poor survival relative to patients whose tumors are SPARC negative.
In this trial, patients with advanced pancreatic cancer with no prior chemotherapy except as a radiation sensitizer received escalating doses of nab-paclitaxel (ABRAXANE®) from 100 mg/m2 to 150 mg/m2 combined with 1000 mg/m2 of gemcitabine. Researchers from TGen/SHC, Johns Hopkins, University of Alabama, and South Texas Hematology/ Oncology reported on the first 20 patients who received 100 mg/m2 of nab-paclitaxel. The study will eventually include 42 patients. Investigators assessed tumor response by measuring levels of the cancer marker CA 19-9 and by PET and/or CAT scan. A drop in CA 19-9 levels has been previously linked in other research with improved survival.
Of the original 20 patients enrolled at the nab-paclitaxel 100 mg/m2 dose, 17 had levels of CA 19-9 that could be evaluated. CA 19-9 levels dropped more than 20 percent in 82 percent of patients, researchers report. Reductions in CA 19-9 of more than 70 percent were observed in 64 percent of patients. Utilizing CAT scan criteria, 9 of the 16 patients (56 percent) who had serial scans had partial responses. Twelve of the 16 patients (75 percent) had partial responses or stable disease for more than four months. SPARC data were available in 12 patients for which response data were available. Six of 8 (75 percent) SPARC positive patients responded to treatment while only 1 of 4 (25 percent) SPARC negative patients responded to treatment.
Side effects were considered tolerable. The most common side effect was low blood counts, followed by fatigue and occasional peripheral neuropathy (numbness and/or tingling of hands and feet).
Based on these results, Abraxis plans to conduct additional studies to evaluate the safety and efficacy of ABRAXANE® in patients with first and second-line pancreatic cancer.