Clinical Trial: 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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Trial of the Combination of Vismodegib GDC-0449 and Erlotinib +/- Gemcitabine

Brief Summary: This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with GDC-0449 with or without gemcitabine hydrochloride in treating patients with metastatic pancreatic cancer or solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as GDC-0449 and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving GDC-0449 together with erlotinib hydrochloride with or without gemcitabine hydrochloride may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 emi
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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.


Original Primary Outcome: Maximum tolerated dose of erlotinib hydrochloride when administered with Hedgehog antagonist GDC-0449

Current Secondary Outcome:

  • 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.
  • 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 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 ]
  • Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Up to 3 months after completion of study treatment ]
  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months after completion of study treatment ]
  • 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 ]


Original Secondary Outcome:

  • Adverse events as assessed by NCI CTCAE v3.0
  • Response as assessed by modified RECIST criteria
  • Effect of treatment on selected biomarkers in circulating tumor cells and tumor biopsies
  • Effect of treatment on fludeoxyglucose F 18 positron emission tomography imaging
  • Association between clinical (toxicity and/or tumor response or activity) and biologic (pharmacodynamic) results


Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 7, 2009
Date Started: March 2009
Date Completion:
Last Updated: January 31, 2017
Last Verified: November 2016