Ensayos clínicos

Inclusion Criteria

• Histologic proof of a solid tumor that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
• Metastatic adenocarcinoma of the pancreas amenable to biopsies (cohort II MTD only)
• Absolute neutrophil count (ANC) ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Total bilirubin ≤ upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3 times upper limit of normal (ULN)
• Creatinine ≤ 1.5 times ULN
• Hemoglobin ≥ 9.0 g/dL
• International Normalized Ratio (INR) within normal limits (for patients treated at the MTD)
• Ability to provide informed consent
• Willing to return to Mayo Clinic for follow up
• Life expectancy ≥ 12 weeks
• Willing to provide the biologic specimens as required by the protocol
• Negative serum pregnancy test done ≤ 7 days prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Able to swallow or have medication administered through a G-tube and absorb the medication
• Agrees to use an acceptable form of contraception, which are
  • 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 (IUD) (non-progesterone T)
  • Vaginal sponge (containing spermicide)
  • 100% commitment to abstinence
• Unacceptable forms of contraception for women of childbearing potential
  • Oral contraception containing progestins only
  • IUD progesterone T
  • Female condom
  • Natural family planning (rhythm method) or breastfeeding
  • Fertility awareness
  • Withdrawal
  • Cervical shield
• Willing to abstain from smoking
• Willing to complete a daily pill diary

Exclusion Criteria

• 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
  • 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 therapy regardless of interval since last treatment
• New York Heart Association classification III or IV
• Seizure disorder
• Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, and use of steroids, or seizure disorder
• Pregnant
• Nursing
• Of childbearing potential and unwilling to employ adequate contraception until 12 months after last study drug dose
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
• Current therapy with a CYP3A4 inhibitor or inducer
• Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy treatment
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • If a history of prior malignancy, must not be receiving other specific treatment (other than hormonal therapy) for 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)
• More than 2 prior chemotherapy regimens for the current metastatic malignancy
  • Full dose chemotherapy used in conjunction with concurrent radiation therapy will be included as prior therapy
  • Prior hormonal therapy (e.g. leuprolide, aromatase inhibitors, tamoxifen) will be allowed and not included as a prior chemotherapy
• Previous therapy with a hedgehog inhibitor