TD2 CASE STUDIES

August 25, 2011

PCRT Case Study: Setting a New Standard for Pancreas Cancer

A Phase I-II study using gemcitabine + nab-paclitaxel in advanced Pancreatic Cancer Patients

The Challenge:

Pancreatic cancer is the fourth leading cause of cancer death and has devastatingly low 1 and 5 year survivorship rates. Here's how are team is making a difference:

The Solution:

In 2006, the Pancreatic Cancer Research Team (PCRT), led by Dr. Manuel Hidalgo and Dr. Dan Von Hoff, opened a Phase I-II clinical trial using gemcitabine and nab-paclitaxel (Abraxane) for advanced pancreatic cancer patients. Previous evidence had shown in mice that nab-paclitaxel was drawn by SPARC (Secreted protein acidic and rich in cysteine), which was highly expressed in pancreatic tumors. Abraxane is currently approved for breast cancer but the PCRT team thought that using nab-paclitaxel in combination with gemcitabine would increase the delivery of these agents directly to the tumor because of the attraction of the albumin coating of the nab-paclitaxel to SPARC in the tumor.

Four PCRT Sites opened the study and the trial enrolled a total of 67 patients, which included a Phase I portion of 23 patients where the dose of the combination of the two drugs was established. The remaining 44 patients were enrolled at the optimal dose of the combination.

The Result:

This dose combination proved to be very effective on the patients' tumors-shrinking both the primary tumors and live metastases -sometimes eliminating the metastases completely.

The patients stayed on treatment twice as long as average, and both their overall survival and one-year survival were doubled compared to standard treatment for this patient population.

The study completed enrollment in 2009, and some patients (4-5) were on active treatment for over 20 months. Initial data was published at ASCO Annual Meeting in 2009, and publication on the full study was published in the Journal of Clinical Oncology in October 2011.

Due to the stellar tumor responses on this combination, the client is now embarking on a 800+ global Phase III International clinical trial of gemcitabine + Abraxane vs. gemcitabine alone in advanced pancreatic cancer patients. This global trial is expected to complete enrollment in early 2012. Over half of the PCRT sites are participating in this large phase III study.

The PCRT Investigators are also working with the client on several other smaller investigative studies using gemcitabine + Abraxane in combination for various stages of disease, and in combination with other agents to enhance the effectiveness seen in this previous study.

Because of the efforts of PCRT Investigators and project managers on the Phase I-II study, the combination of gemcitabine + Abraxane is now widely being used by oncologists to treat advanced pancreatic cancer patients, and it is being used as a backbone to build upon further effective treatments in pancreatic cancer.