NCT01537107

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2012

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 14, 2012

Completed
9 days until next milestone

First Posted

Study publicly available on registry

February 23, 2012

Completed
11 days until next milestone

Study Start

First participant enrolled

March 5, 2012

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 27, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 27, 2018

Completed
Last Updated

April 8, 2019

Status Verified

April 1, 2019

Enrollment Period

6.3 years

First QC Date

February 14, 2012

Last Update Submit

April 4, 2019

Conditions

Acinar Cell Adenocarcinoma of the PancreasDuct Cell Adenocarcinoma of the PancreasRecurrent Pancreatic CancerStage IV Pancreatic CancerUnspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

  • MTD (Cohort I) ) and toxicity profile of combination of vismodegib plus sirolimus every 28 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.

    120 days

Secondary Outcomes (3)

  • 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

    120 days

  • Time to treatment failure

    120 days

  • Antitumor effect of molecularly targeted agents non-invasively by F18-FDG PET or PET/CT (Cohort II)

    120 days

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

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.

Drug: vismodegibDrug: sirolimusProcedure: positron emission tomographyProcedure: computed tomographyOther: pharmacological studyOther: laboratory biomarker analysisRadiation: fludeoxyglucose F 18

Interventions

vismodegibDRUG

Given PO

Also known as: GDC-0449
Treatment (enzyme inhibitor therapy)
sirolimusDRUG

Given PO

Also known as: Rapamune, rapamycin, RAPA
Treatment (enzyme inhibitor therapy)
positron emission tomographyPROCEDURE

Correlative studies

Also known as: FDG-PET, PET, PET scan, tomography, emission computed
Treatment (enzyme inhibitor therapy)
computed tomographyPROCEDURE

Correlative studies

Also known as: tomography, computed
Treatment (enzyme inhibitor therapy)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Treatment (enzyme inhibitor therapy)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (enzyme inhibitor therapy)
fludeoxyglucose F 18RADIATION

Correlative studies

Also known as: 18FDG, FDG
Treatment (enzyme inhibitor therapy)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • COHORT I (DOSE ESCALATION): histologic proof of cancer that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
  • COHORT II (MTD): metastatic adenocarcinoma of the pancreas and tumor amenable to biopsies; prior systemic treatment for metastatic disease is allowed
  • Absolute neutrophil count (ANC) =\> 1500/uL
  • Platelet \>= 100,000/uL
  • Total bilirubin =\< upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x ULN
  • Creatinine =\< 1.5 x ULN
  • Hemoglobin \>= 9.0 g/dL
  • Prothrombin time (PT)/international normalized ratio (INR) \< 1.25 x ULN (Cohort II \[MTD\] only)
  • Cholesterol \< Common Terminology Criteria for Adverse Events (CTCAE) grade 3
  • Triglycerides \< CTCAE grade 2
  • Magnesium \>= lower limit of normal (LLN) and =\< ULN
  • Ability to provide informed consent
  • Willing to return to Mayo Clinic for follow up
  • Life expectancy \>= 12 weeks
  • Cohort II (MTD) only - Translational Research: Willing to provide the biologic specimens as required by the protocol; Note: this is part of the mandatory translational research component
  • +26 more criteria

You may not qualify if:

  • COHORT I (DOSE ESCALATION): Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes mellitus or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies:
  • Chemotherapy =\< 4 weeks prior to registration
  • Mitomycin C/nitrosoureas =\< 6 weeks prior to registration
  • Immunotherapy =\< 4 weeks prior to registration
  • Biologic therapy =\< 4 weeks prior to registration
  • Radiation therapy =\< 4 weeks prior to registration
  • Radiation to \> 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Uncontrolled Seizure Disorder
  • Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, use of steroids, or seizure disorder
  • Any of the following:
  • Pregnant women
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Mayo Clinic Campus in Arizona

Scottsdale, Arizona, United States

Location

Mayo Clinic Campus in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

HhAntag691SirolimusMagnetic Resonance Spectroscopy2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazoleFluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesDeoxyglucoseDeoxy SugarsCarbohydrates

Study Officials

  • Charles Erlichman, M.D.

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 14, 2012

First Posted

February 23, 2012

Study Start

March 5, 2012

Primary Completion

June 27, 2018

Study Completion

June 27, 2018

Last Updated

April 8, 2019

Record last verified: 2019-04

Locations

US(3)