Sirolimus and Vismodegib in Treating Patients With Solid Tumors or Pancreatic Cancer That is Metastatic or Cannot Be Removed By Surgery
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Procedure: positron emission tomography
Procedure: computed tomography
Other: pharmacological study
Other: laboratory biomarker analysis
Radiation: fludeoxyglucose F 18
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of The Combination of Vismodegib and Sirolimus|
- MTD (Cohort I) ) and toxicity profile of combination of vismodegib plus sirolimus every 28 days. [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). DLT will be defined as a course 1 adverse event (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) attributed (definitely, probably, or possibly) to the study treatment. MTD will be examined in an exploratory and hypothesis generating fashion.
- Adverse events (AEs) profile in terms of the number and severity of all adverse events (overall, by dose-level, and by tumor group) at baseline, at each dose level and at 30 days after completion of study treatment [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
- Time to treatment failure [ Time Frame: 120 days ] [ Designated as safety issue: No ]
- Antitumor effect of molecularly targeted agents non-invasively by F18-FDG PET or PET/CT (Cohort II) [ Time Frame: 120 days ] [ Designated as safety issue: No ]
|Study Start Date:||March 2012|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive sirolimus PO QD and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: GDC-0449Drug: sirolimus
Other Names:Procedure: positron emission tomography
Other Names:Procedure: computed tomography
Other Name: tomography, computedOther: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Correlative studiesRadiation: fludeoxyglucose F 18
I. To determine the maximally tolerated dose (MTD) of the combination of vismodegib and sirolimus in unresectable solid tumors. (Cohort I)
I. To describe the adverse event profile associated with this treatment combination.
II. To describe the tumor responses to treatment combination.
I. To assess the effect of the sirolimus and vismodegib combination on selected biomarkers in tumor biopsies of patients with metastatic pancreatic cancer.
II. To assess the effect of the combination of vismodegib and sirolimus on fludeoxyglucose F 18 (F18-FDG) positron emission tomography (PET) or PET/computed tomography (CT) imaging in Cohort II (MTD) patients with metastatic pancreatic cancer.
III. To study the association of clinical (toxicity and/or tumor response or activity) with the biologic (pharmacodynamic) results obtained by examining tissue biopsies and PET or PET/CT imaging from the same patients.
OUTLINE: This is a dose-escalation study of sirolimus.
Patients receive sirolimus orally (PO) once daily (QD) and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01537107
|United States, Arizona|
|Mayo Clinic Campus in Arizona|
|Scottsdale, Arizona, United States|
|United States, Florida|
|Mayo Clinic Campus in Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Charles Erlichman, M.D.||Mayo Clinic|