Clinical Trials

Inclusion Criteria:

• 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")
  • Tubal ligation
  • Partner's vasectomy
  • Intrauterine device (non-progesterone T)
  • Vaginal sponge (containing spermicide)
• Other acceptable forms:
  • 100% commitment to abstinence
• Unacceptable forms of contraception for women of childbearing potential:
  • Oral contraception containing progestins only
  • Intrauterine device (IUD) progesterone T
  • Female condom
  • Natural family planning (rhythm method) or breastfeeding
  • Fertility awareness
  • Withdrawal
  • Cervical shield
• Willing not to smoke
• Willing to complete a pill diary each day

Exclusion Criteria:

• 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
• Receiving any medications or substances that are inducers of CYP450 2C8
  • Inducer of CYP2C8: Rifampin
• Receiving any medications or substances that are strong or moderate inhibitors of CYP450 CYP2C9
  • Strong or Moderate Inhibitors of CYP2C9: Fluconazole, Amiodarone
• Receiving any medications or substances that are inducers of CYP450 2C9
  • Inducers of CYP2C9: Rifampin, Secobarbital
• Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy (HAART) treatment
• Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in situ (e.g. of cervix, breast prostate); if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
• Prior therapy with a hedgehog inhibitor