Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas
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|ClinicalTrials.gov Identifier: NCT01088815|
Recruitment Status : Completed
First Posted : March 17, 2010
Results First Posted : April 26, 2019
Last Update Posted : April 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Pancreatic Cancer||Drug: Gemcitabine, nab-Paclitaxel, GDC-0449||Phase 2|
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 event rate.
Following the determination of eligibility patients will receive the following treatment:
- One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||98 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 17, 2010|
|Actual Primary Completion Date :||December 1, 2017|
|Actual Study Completion Date :||February 17, 2018|
Experimental: Gemcitabine, nab-paclitaxel, GDC-0449
Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib)
Drug: Gemcitabine, nab-Paclitaxel, GDC-0449
- Progression Free Survival With the Combination of GDC-0449 With Gemcitabine and Nab-paclitaxel. [ Time Frame: 6 years ]Number of months from time first therapy received to the earliest documented disease progression or death from any cause.
- Safety of Combination Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas as Assessed by Number of Grade 3 or 4 Adverse Events [ Time Frame: 6 years ]Number of grade 3 or 4 adverse events as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v4.0) that occur after Cycle 2, Day 1
- Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Overall Survival [ Time Frame: 6 years ]Total number of months alive.
- Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Tumor Response [ Time Frame: 6 years ]Number of participants with complete (CR) or partial (PR) response as defined by RECIST criteria.
- Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Changes in Pancreatic Cancer Stem Cell [ Time Frame: 6 years ]Change in number of Pancreatic cancer stem cells in tissue and peripheral blood in tissue biopsy and peripheral blood.
- Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Hedgehog Signaling Pathway Downregulation [ Time Frame: 6 years ]Hedgehog signaling pathway downregulation as measured by Gli-1 and Patch expression
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01088815
|United States, Arizona|
|Translational Genomics Research Institute (TGen)|
|Scottsdale, Arizona, United States, 85258|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21205|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Daniel Laheru, MD||Sidney Kimmel Comprehensive Cancer Center JHMI|
|Principal Investigator:||Ana De Jesus-Acosta, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|