A Study of Vismodegib in Patients With Advanced Solid Malignancies Including Hepatocellular Carcinoma With Varying Degrees of Renal or Hepatic Function
Condition: Cancer
MeSH terms: Carcinoma, Hepatocellular
Intervention: Vismodegib
Intervention description: oral repeating dose of 150 mg once daily
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a Phase Ib, open-label, multiple-center, multiple-dose study designed to evaluate the
      pharmacokinetics and safety of vismodegib in patients with advanced solid malignancies
      (including hepatocellular carcinoma and lymphoma) that are refractory to standard therapy or
      for whom no standard therapy exists.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed advanced solid malignancy (including
             hepatocellular carcinoma and lymphoma) that is metastatic or unresectable and for
             which standard curative or palliative measures do not exist or are no longer effective

          -  Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/=60%)

          -  Acceptable bone marrow functions

          -  Normal or varying degrees of renal or hepatic impairment according to NCI Organ
             Dysfunction Working Group criteria.

          -  Organ function should be stable for at least 2 weeks before Day 1. In addition, there
             should be no evidence of acute exacerbation of hepatic/renal disease.

          -  Patients with gliomas or known brain metastases who require corticosteroids or
             anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1
             month prior to enrollment. Patients with known brain metastases must be at least 4
             weeks out from any radiation before starting the protocol (Day 1).

          -  Documented negative serum pregnancy test for women of childbearing potential

          -  For women of childbearing potential, agreement to the use of two acceptable methods of
             contraception during the study and for 7 months after discontinuation of vismodegib

          -  For men with female partners of childbearing potential, agreement to use a latex,
             non-latex, or any other male condom and to advise their female partners to use an
             additional acceptable method of birth control during the study and for 2 months after
             discontinuation of study drug

          -  Agreement not to donate blood/blood products during the study and for 7 months after
             discontinuing study drug

          -  For men with normal renal and hepatic function, agreement to provide semen during the
             vismodegib treatment period for study assessment (optional), but otherwise NOT to
             donate semen during the vismodegib treatment period and for 2 months after
             discontinuation of study drug

        Exclusion Criteria:

          -  Pregnancy or lactation

          -  Chemotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks
             for nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Investigational agents within 28 days prior to study entry (Day 1)

          -  Use of Pgp inhibitors within 7 days of Day 1

          -  Use of gastric pH altering drugs except antacids within 7 days of Day 1

          -  Major surgery within 14 days prior to treatment (Day 1). Patients with recent major
             surgery must have recovered from that surgery. Patients who are expected to have any
             major surgery during the study treatment period should not be enrolled.

          -  Uncontrolled concurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements. History of other diseases, metabolic dysfunction, physical
             examination finding, or clinical laboratory finding giving reasonable suspicion of a
             disease or condition that contraindicates use of vismodegib or that might affect
             interpretation of the results from this study or renders the patient at high risk from
             treatment complications.

          -  Severely impaired renal function (Cohort 2 only) should not have active hemolysis, and
             should not be on hemodialysis or peritoneal dialysis during the screening and study
             treatment period (Days 1-9).