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

Completed · Phase 1

Conditions studied: 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

In brief

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

Key facts

Study ID: NCT01537107
Run by: Mayo Clinic
People needed: 31
Starts: 2012-03-05
Expected to finish: 2018-06-27
Last updated by the study team: 2019-04-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
Women of childbearing potential only: Negative serum pregnancy test done =< 7 days prior to registration; NOTE: female subjects who are pregnant or nursing are excluded from this study; there is no specific mitigation strategy for vismodegib toxicity; however, male patients should be made aware of it during the consent process; although this effect is expected to be reversible with discontinuation of dosing, long-term effects on male fertility cannot be excluded at this time
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Able to swallow or have medication administered through a G-tube and absorb the medication
Participant agrees to use acceptable form of contraception during the study and for up to 7 months after last study drug dose
Acceptable forms of contraception:
Latex condom (always used with spermicide)
Diaphragm (always used with spermicide)
Cervical cap (always used with spermicide)
Acceptable forms of secondary contraception, when used along with a barrier method:
Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. "Mini-pill")

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
Nursing women
This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CPY450 3A4); use of the following strong or moderate inhibitors are prohibited:
Strong Inhibitors of CYP3A4: Indinavir, Nelfinavir, Ritonavir, Clarithromycin, Itraconazole, Ketoconazole, Nefazodone, Saquinavir, Telithromycin
Moderate Inhibitors of CYP3A4: Aprepitant, Erythromycin, Fluconazole, Grapefruit juice, Verapamil, Diltiazem
Receiving any medications or substances that are inducers of CYP450 3A4
Inducers of CYP3A4: Efavirenz, Nevirapine, Carbamazepine, Modafinil, Phenobarbital, Phenytoin, Pioglitazone, Rifabutin, Rifampin, St. John's wort
Receiving any medications or substances that are strong or moderate inhibitors of CYP450 CYP2C8
Strong or Moderate Inhibitors of CYP2C8: Gemfibrozil, Trimethoprim

Where it is running

Mayo Clinic Campus in Arizona — Scottsdale, Arizona, United States
Mayo Clinic Campus in Florida — Jacksonville, Florida, United States
Mayo Clinic — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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