Clinical Trial: Sirolimus and Vismodegib in Treating Patients With Solid Tumors or Pancreatic Cancer That is Metastatic or Cannot Be Removed By Surgery

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: Phase I Trial of The Combination of Vismodegib and Sirolimus

Brief Summary: This phase I trial studies the side effects and the best dose of sirolimus when given together with vismodegib in treating patients with solid tumors or pancreatic cancer that is metastatic or cannot be removed by surgery. Sirolimus and vismodegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) of the combination of vismodegib and sirolimus in unresectable solid tumors. (Cohort I)

SECONDARY OBJECTIVES:

I. To describe the adverse event profile associated with this treatment combination.

II. To describe the tumor responses to treatment combination.

CORRELATIVE OBJECTIVES:

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.


Sponsor: Mayo Clinic

Current Primary Outcome: MTD (Cohort I) ) and toxicity profile of combination of vismodegib plus sirolimus every 28 days. [ Time Frame: 120 days ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]
  • Time to treatment failure [ Time Frame: 120 days ]
  • Antitumor effect of molecularly targeted agents non-invasively by F18-FDG PET or PET/CT (Cohort II) [ Time Frame: 120 days ]


Original Secondary Outcome: Same as current

Information By: Mayo Clinic

Dates:
Date Received: February 14, 2012
Date Started: March 2012
Date Completion: December 2017
Last Updated: March 21, 2017
Last Verified: March 2017