Phase I Trial of the Combination of Vismodegib GDC-0449 and Erlotinib +/- Gemcitabine
I. To determine the maximum tolerated dose of erlotinib hydrochloride and Hedgehog
antagonist GDC-0449 with or without gemcitabine hydrochloride in patients with unresectable
I. To describe the adverse events profile associated with these treatment regimens.
II. To describe the responses in patients treated with these regimens. III. To assess the
effect of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 on selected biomarkers in
circulating tumor cells and tumor biopsy samples from patients with metastatic pancreatic
IV. To assess the effect of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 on
fludeoxyglucose F 18 positron emission tomography imaging in patients with metastatic
V. To study the association between clinical (toxicity and/or tumor response or activity)
and biologic (pharmacodynamic) results associated with erlotinib hydrochloride and Hedgehog
antagonist GDC-0449 in patients with metastatic pancreatic cancer.
OUTLINE: This is a dose-escalation study of erlotinib hydrochloride.
Patients receive Hedgehog antagonist GDC-0449 orally (PO) once daily (QD) and erlotinib
hydrochloride PO QD on days 1-28. Some patients also receive gemcitabine hydrochloride IV
over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Patients treated at the maximum tolerated dose undergo fludeoxyglucose F 18 positron
emission tomography at baseline and on day 28. These patients also undergo tumor tissue and
blood sample collection at baseline and periodically during study for correlative laboratory
studies. Samples are analyzed for tyrosine phosphorylated or total MAP-K, EGFR, AKT, and
other potential biomarkers of activity/response and for levels of genes transcriptionally
activated (e.g., BCL-2, GLI, BFL-1/A1, 4-1BB, PTC1) by immunofluorescence, IHC, and
After completion of study therapy, patients are followed at 3 months.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of erlotinib hydrochloride defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients
DLT will be defined as an adverse event, according to CTCAE version 3.0, attributed (definitely, probably, or possibly to the study treatment.
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|
|M D Anderson Cancer Center- Orlando||Orlando, Florida 32806|