A Phase II Study of Gemcitabine and Nab-Paclitaxel in Combination With GDC-0449 (Hedgehog Inhibitor) in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas
The emergence of new small molecules with capacity of blocking the Hedgehog signaling
pathway provides a novel therapeutic approach in pancreatic adenocarcinoma treating the
primary tumor, stroma, systemic metastases and pancreatic cancer stem cells by hedgehog
pathway inhibition. This phase 2 clinical trial will evaluate the progression free survival
(PFS) in patients with previously untreated metastatic pancreatic adenocarcinoma. We
hypothesize that the combination of cytotoxic agents (gemcitabine and nab-paclitaxel) with
the Hedgehog inhibitor GDC-0449 may increase PFS.
This study includes correlative studies to attempt to understand the stem cell biology and
mechanism for any observed clinical benefits with the use of Hedgehog inhibitor GDC-0449.
These include changes in the hedgehog pathway and changes in pancreatic cancer stem cell
markers with pre and post treatment biopsies. The safety of GDC-0449 when combined with
chemotherapy gemcitabine and nab-paclitaxel will also be assessed by evaluating adverse
Following the determination of eligibility patients will receive the following treatment:
1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15
(28 days cycle) then
2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days
cycle in combination with oral GDC-0449 150 mg daily
Patients may continue on treatment regimen until they experience progressive disease or
unacceptable toxicity, require palliative radiotherapy, withdraw consent or the physician
feels it is not longer in their best interest to continue on treatment.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the progression free survival with the combination of GDC-0449 with Gemcitabine and nab-paclitaxel.
• Progression free survival
Daniel Laheru, MD
Sidney Kimmel Comprehensive Cancer Center JHMI
United States: Institutional Review Board
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|
|Translational Genomics Research Institute (TGen)||Scottsdale, Arizona 85258|