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

NCT01546519 | Completed Phase 1 Results

• 1 other identifier: GP27839
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

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.

Conditions

Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib

  Maximum observed plasma Concentration (Cmax) \& Concentration at steady-state (Css) following multiple doses of vismodegib (150 mg QD) were analyzed. At steady state the amount of drug administered (in a given time period) is equal to the amount of drug eliminated. Blood samples for assessing Cmax and Css for analysis were collected following multiple oral doses of vismodegib at pre-dose and at 0.5, 1, 2, 4, 8 and 24 hours post-dose on Day 8. From the plasma concentration-time curve, the PK parameter Cmax and Css were determined by standard non-compartmental analysis using WinNonlin

  Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8

• The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib

  The steady state pharmacokinetic profile following oral administration of multiple doses of vismodegib included determining the area under the curve over the dosing interval (AUC\[0-24 hours\]). The AUC\[0-24 hrs\]) was determined by standard non-compartmental analysis using WinNonlin. Blood samples were collected at pre-dose and at 0.5, 1, 2, 4, 8 and 24 hours post-dose on Day 8 to estimate AUC(0-24 hrs).

  Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8

Secondary Outcomes (7)

• The Percentage of Dose of Vismodegib in 24-hour Total Urine

  24 hr total interval on Day 8

• Renal Clearance of Vismodegib

  0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8

• Amount of Vismodegib Excreted Into Urine in 24 Hours (Ae0-24hr)

  24 hr total interval on Day 8

• Time to Maximum Plasma Concentration (Tmax) of Vismodegib

  Up to 8 days

• Minimum Plasma Concentration (Cmin) of Vismodegib

  Up to 8 days

Study Arms (5)

1

EXPERIMENTAL

Control cohort with normal renal and normal hepatic function

Drug: Vismodegib

2

EXPERIMENTAL

Severe renal impairment and normal hepatic function

Drug: Vismodegib

3

EXPERIMENTAL

Mild hepatic impairment and normal renal function

Drug: Vismodegib

4

EXPERIMENTAL

Moderate hepatic impairment and normal renal function

Drug: Vismodegib

5

EXPERIMENTAL

Severe hepatic impairment and normal renal function

Drug: Vismodegib

Interventions

Vismodegib DRUG

oral repeating dose of 150 mg once daily

1; 2; 3; 4; 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (5)

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Baltimore, Maryland, 21201, United States

Location

Unknown Facility

Detroit, Michigan, 48201, United States

Location

Unknown Facility

Lebanon, New Hampshire, 03756, United States

Location

Unknown Facility

New York, New York, 10017, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

HhAntag691

Results Point of Contact

• Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 61 6878333

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2012
• First Posted: March 7, 2012
• Study Start: March 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-04

Locations

US (5)