GDC-0449 and Erlotinib Hydrochloride With or Without Gemcitabine Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer or Solid Tumors That Cannot Be Removed by Surgery
|ClinicalTrials.gov Identifier: NCT00878163|
Recruitment Status : Active, not recruiting
First Posted : April 8, 2009
Last Update Posted : March 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Pancreatic Acinar Cell Carcinoma Pancreatic Ductal Adenocarcinoma Recurrent Pancreatic Carcinoma Stage IV Pancreatic Cancer AJCC v6 and v7||Other: Diagnostic Laboratory Biomarker Analysis Drug: Erlotinib Hydrochloride Drug: Gemcitabine Hydrochloride Drug: Vismodegib||Phase 1|
I. To determine the maximum tolerated dose of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 with or without gemcitabine hydrochloride in patients with unresectable solid tumors.
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 cancer.
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 pancreatic cancer.
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 quantitative-PCR.
After completion of study therapy, patients are followed at 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of the Combination of Vismodegib GDC-0449 and Erlotinib +/- Gemcitabine|
|Actual Study Start Date :||March 31, 2009|
|Primary Completion Date :||April 1, 2012|
Experimental: Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)
Patients receive Hedgehog antagonist GDC-0449 PO 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.
Other: Diagnostic Laboratory Biomarker Analysis
Correlative studiesDrug: Erlotinib Hydrochloride
Other Names:Drug: Gemcitabine Hydrochloride
Other Names:Drug: Vismodegib
- 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 [ Time Frame: 28 days ]DLT will be defined as an adverse event, according to CTCAE version 3.0, attributed (definitely, probably, or possibly to the study treatment.
- Adverse events as assessed by NCI CTCAE v3.0 [ Time Frame: Up to 3 months after completion of study treatment ]The number and severity of all adverse events (overall, and by dose-level) will be tabulated and summarized.
- Toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, graded using the NCI CTCAE version 3.0 [ Time Frame: Up to 3 months after completion of study treatment ]
- Response as assessed by modified RECIST criteria [ Time Frame: Up to 3 months after completion of study treatment ]Summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.
- Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months after completion of study treatment ]
- Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Up to 3 months after completion of study treatment ]
- Time to progression [ Time Frame: Up to 3 months after completion of study treatment ]
- Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months after completion of study treatment ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00878163
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|UF Cancer Center at Orlando Health|
|Orlando, Florida, United States, 32806|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Charles Erlichman||Mayo Clinic|