Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas - Full Text View

Purpose

This is an open-label, single arm, multi-center, Phase II trial to evaluate the progression free survival in patients with metastatic adenocarcinoma of the pancreas treated with a hedgehog inhibitor (GDC-0449) in combination with chemotherapy (gemcitabine and nab-Paclitaxel).

Condition	Intervention	Phase
Metastatic Pancreatic Cancer	Drug: Gemcitabine, nab-Paclitaxel, GDC-0449	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Digestive Diseases Pancreatic Cancer Pancreatic Diseases

Drug Information available for: Pancreatin Paclitaxel Pancrelipase Gemcitabine Gemcitabine hydrochloride Vismodegib

U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:

To evaluate the progression free survival with the combination of GDC-0449 with Gemcitabine and nab-paclitaxel. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Progression free survival
To evaluate the safety of this combination in patients with metastatic adenocarcinoma of the pancreas. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events

Secondary Outcome Measures:

To evaluate other efficacy measures and the changes in the pancreatic cancer stem cells with the combination of GDC-0449 with gemcitabine and nab-Paclitaxel. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Overall survival
- Tumor response
- Pancreatic cancer stem cells in tissue and peripheral blood
- Hedgehog signaling pathway downregulation

Estimated Enrollment:	80
Study Start Date:	September 2010
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Intervention Details:

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

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cells tumors are excluded. Biopsy within 14 days of starting treatment.
Patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
Patient has NOT received previous radiotherapy, surgery or chemotherapy or investigational drug therapy for the treatment of metastatic disease. If the patient received radiotherapy, chemotherapy or investigational therapy in the adjuvant setting it should be completed 3 weeks prior to enrollment. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least six months after completing the last dose of gemcitabine
Age >18 years.
Life expectancy of greater than 1 month.
ECOG performance status 0 or 1 (Karnofsky >70%).
Patients must have adequate organ and marrow function

Exclusion Criteria:

Patient had received chemotherapy or radiotherapy for metastatic disease
Patient is receiving other investigational agents.
Patient has known brain metastases, unless previously treated and well controlled for at least three months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study.
Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.
Uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure not controlled with medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded
Patient has undergone a major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ) within four weeks prior to Day 1 of treatment on this study.
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088815

Locations

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

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

Stand Up To Cancer

Genentech

Celgene Corporation

Investigators

Principal Investigator:	Daniel Laheru, MD	Sidney Kimmel Comprehensive Cancer Center JHMI
Principal Investigator:	Ana De Jesus-Acosta, MD	Sidney Kimmel Comprehensive Cancer Center

More Information

No publications provided

Responsible Party:	Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01088815 History of Changes
Other Study ID Numbers:	J1013, NA_00036883
Study First Received:	March 1, 2010
Last Updated:	September 20, 2012
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:

Adenocarcinoma
Hedgehog
Neoplasms
Digestive System Diseases
Neoplasms by Site

Digestive System Neoplasms
Neoplasms by Histologic Type
Pancreatic Neoplasms
Pancreatic Diseases
Carcinoma

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Pancrelipase

Gemcitabine
Paclitaxel
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 18, 2013