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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

Phase 2
18 Years
Open (Enrolling)
Metastatic Pancreatic Cancer

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Trial Information

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
event rate.

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.

Inclusion Criteria:

1. 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.

2. 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.

3. 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

4. Age >18 years.

5. Life expectancy of greater than 1 month.

6. ECOG performance status 0 or 1 (Karnofsky >70%).

7. Patients must have adequate organ and marrow function

Exclusion Criteria:

1. Patient had received chemotherapy or radiotherapy for metastatic disease

2. Patient is receiving other investigational agents.

3. 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)

4. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GDC-0449 or other agents used in the study.

5. Patients taking medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.

6. 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.

7. Pregnant women are excluded

8. 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.

9. 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

Type of Study:


Study Design:

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

Outcome Measure:

To evaluate the progression free survival with the combination of GDC-0449 with Gemcitabine and nab-paclitaxel.

Outcome Description:

• Progression free survival

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Daniel Laheru, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center JHMI


United States: Institutional Review Board

Study ID:

J1013, NA_00036883



Start Date:

September 2010

Completion Date:

Related Keywords:

  • Metastatic Pancreatic Cancer
  • Adenocarcinoma
  • Hedgehog
  • Neoplasms
  • Digestive System Diseases
  • Neoplasms by Site
  • Digestive System Neoplasms
  • Neoplasms by Histologic Type
  • Pancreatic Neoplasms
  • Pancreatic Diseases
  • Carcinoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms



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