A Study of the Hedgehog Pathway Inhibitor Vismodegib in Patients With Advanced Solid Malignancies Including Hepatocellular Carcinoma With Varying Degrees of Renal or Hepatic Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01546519
First received: March 2, 2012
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Solid Cancers
Drug: Vismodegib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]
  • Steady-state area under the plasma concentration-time curve (AUC0-24hr) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to maximum plasma concentration (Tmax) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]
  • Minimum plasma concentration (Cmin) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]
  • Apparent clearance (CL/F) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]
  • Amount of vismodegib in 24-hour total urine, and renal clearance (CLR) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]
  • Apparent non-renal clearance (CLNR/F) [ Time Frame: up to 8 days ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: March 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Control cohort with normal renal and normal hepatic function
Drug: Vismodegib
oral repeating dose
Experimental: 2
Severe renal impairment and normal hepatic function
Drug: Vismodegib
oral repeating dose
Experimental: 3
Mild hepatic impairment and normal renal function
Drug: Vismodegib
oral repeating dose
Experimental: 4
Moderate hepatic impairment and normal renal function
Drug: Vismodegib
oral repeating dose
Experimental: 5
Severe hepatic impairment and normal renal function
Drug: Vismodegib
oral repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546519

Locations
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Maryland
Baltimore, Maryland, United States, 21201
United States, Michigan
Detroit, Michigan, United States, 48201
United States, New Hampshire
Lebanon, New Hampshire, United States, 03756
United States, New York
New York, New York, United States, 10065
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01546519     History of Changes
Other Study ID Numbers: GP27839
Study First Received: March 2, 2012
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 18, 2014