Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas
Condition: Metastatic Pancreatic Cancer
MeSH terms: Adenocarcinoma
Intervention: Gemcitabine, nab-Paclitaxel, GDC-0449
Intervention description: 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
Intervention MeSH terms: Paclitaxel; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 98.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adenocarcinoma; Hedgehog; Neoplasms; Digestive System Diseases; Neoplasms by Site; Digestive System Neoplasms; Neoplasms by Histologic Type; Pancreatic Neoplasms; Pancreatic Diseases; Carcinoma

Summary:

      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).
    

Eligibility criteria:

        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