Clinical trial NCT01546519: A Study of Vismodegib in Patients With Advanced Solid Malignancies Including Hepatocellular Carcinoma With Varying Degrees of Renal or Hepatic Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Primary outcomes:
measure: Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib
timeFrame: Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8
measure: The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib
timeFrame: Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8
Secondary outcomes:
measure: The Percentage of Dose of Vismodegib in 24-hour Total Urine
timeFrame: 24 hr total interval on Day 8
measure: Renal Clearance of Vismodegib
timeFrame: 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8
measure: Amount of Vismodegib Excreted Into Urine in 24 Hours (Ae0-24hr)
timeFrame: 24 hr total interval on Day 8
measure: Time to Maximum Plasma Concentration (Tmax) of Vismodegib
timeFrame: Up to 8 days
measure: Minimum Plasma Concentration (Cmin) of Vismodegib
timeFrame: Up to 8 days
measure: Apparent Clearance (CL/F) of Vismodegib
timeFrame: Up to 8 days
measure: Apparent Non-renal Clearance (CLNR/F) of Vismodegib
timeFrame: Up to 8 days
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Lebanon
country: United States
state: New Hampshire
city: New York
country: United States
state: New York
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: