A Phase Ib Open-Label Pharmacokinetics and Safety Study of the Hedgehog Pathway Inhibitor Vismodegib in Patients With Advanced Solid Malignancies Including Hepatocellular Carcinoma With Varying Degrees of Renal or Hepatic Function
- 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
- 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
- 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
- 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
- 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).