CancerPhase 1NCT01546519

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

A Phase 1 study testing Vismodegib in people with Cancer, run by Genentech, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Cancer
What is being tested?: Vismodegib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 5 sitesUnited States
Study dates: Mar 2012to Apr 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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).

Show all 11Show fewer

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

Who cannot join

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).

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Study site
Baltimore, Maryland, 21201
Study site
Chicago, Illinois, 60637
Study site
Detroit, Michigan, 48201
Study site
Lebanon, New Hampshire, 03756
Study site
New York, New York, 10017

Other trials in United States

About this study

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

Conditions: Cancer
Being tested: Vismodegib
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VismodegibDrug
oral repeating dose of 150 mg once daily

Study groups in NCT01546519
Study group	Role	What they receive
1	Experimental	Control cohort with normal renal and normal hepatic function Receives: Drug: Vismodegib
2	Experimental	Severe renal impairment and normal hepatic function Receives: Drug: Vismodegib
3	Experimental	Mild hepatic impairment and normal renal function Receives: Drug: Vismodegib
4	Experimental	Moderate hepatic impairment and normal renal function Receives: Drug: Vismodegib
5	Experimental	Severe hepatic impairment and normal renal function Receives: Drug: Vismodegib

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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).
Measured: 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
The percentage of dose vismodegib excreted in urine over a 24-hr total interval was estimated
Measured: 24 hr total interval on Day 8
Renal Clearance of Vismodegib
Renal clearance (CLR) is defined as the apparent total clearance of the drug from plasma after oral administration.
Measured: 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)
The amount of total vismodegib excreted in urine over a 24-hr total interval (Ae0-24hr) was estimated.
Measured: 24 hr total interval on Day 8
Time to Maximum Plasma Concentration (Tmax) of Vismodegib
Tmax is the time to reach maximum plasma concentration of vismodegib. This was a pre-specified PK parameter. However, due to minimal fluctuation of Vismodegib concentrations at steady state, this parameter could not be determined.
Measured: Up to 8 days
Minimum Plasma Concentration (Cmin) of Vismodegib
Cmin is defined as the minimum observed plasma concentration of Vismodegib. This was a pre-specified PK parameter. However, due to minimal fluctuation of Vismodegib concentrations at steady state, this parameter could not be determined.
Measured: Up to 8 days
Apparent Clearance (CL/F) of Vismodegib
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr). This was a pre-specified PK parameter. However, due to minimal fluctuation of vismodegib concentrations at steady state, this parameter could not be determined.
Measured: Up to 8 days
Apparent Non-renal Clearance (CLNR/F) of Vismodegib
Apparent Non-Renal Clearance (CLNR) describes the removal of vismodegib by organs other than the kidneys. This was a pre-specified PK parameter. However, due to minimal fluctuation of vismodegib concentrations at steady state, this parameter could not be determined.
Measured: Up to 8 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2012Apr 2014

First posted7 Mar 2012 (estimated)
Study startMar 2012
Primary completionApr 2014
Study completionApr 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for CancerStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01546519
Sponsor's protocol ID: GP27839
Status last verified: Apr 2016
First submitted: 2 Mar 2012
Last updated: 23 May 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01546519
Acronym / sponsor ID: GP27839
Conditions: Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Mar 2012
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 7 Mar 2012 (estimated)
Results: Posted 23 May 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
1	Experimental	Drug: VismodegibControl cohort with normal renal and normal hepatic function
2	Experimental	Drug: VismodegibSevere renal impairment and normal hepatic function
3	Experimental	Drug: VismodegibMild hepatic impairment and normal renal function
4	Experimental	Drug: VismodegibModerate hepatic impairment and normal renal function
5	Experimental	Drug: VismodegibSevere hepatic impairment and normal renal function

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Vismodegiboral repeating dose of 150 mg once daily	Drug	1, 2, 3, 4, 5

Primary outcome

Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib
Time frame: Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8
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
The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib
Time frame: Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8
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).

7 secondary outcomes

The Percentage of Dose of Vismodegib in 24-hour Total Urine
Time frame: 24 hr total interval on Day 8
Renal Clearance of Vismodegib
Time frame: 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)
Time frame: 24 hr total interval on Day 8
Time to Maximum Plasma Concentration (Tmax) of Vismodegib
Time frame: Up to 8 days
Minimum Plasma Concentration (Cmin) of Vismodegib
Time frame: Up to 8 days
Apparent Clearance (CL/F) of Vismodegib
Time frame: Up to 8 days
Apparent Non-renal Clearance (CLNR/F) of Vismodegib
Time frame: Up to 8 days

Results and safety

Results posted to the registry on 23 May 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control Cohort With Normal Renal and Normal Hepatic Function	9	0
Mild Hepatic Impairment and Normal Renal Function (Mild HI)	8	0
Moderate Hepatic Impairment and Normal Renal Function (Mod HI)	8	0
Severe Hepatic Impairment and Normal Renal Function (Sev HI)	6	0

Primary outcome: Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib

Time frame: Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8. Mean (Standard Deviation). Unit: micromolar

Measure	Control Cohort With Normal Renal and Normal Hepatic Function n = 9	Mild Hepatic Impairment and Normal Renal Function (Mild HI) n = 8	Moderate Hepatic Impairment and Normal Renal Function (Mod HI) n = 6	Severe Hepatic Impairment and Normal Renal Function (Sev HI) n = 3
Cmax	23.6 (9.39)	30.7 (13.10)	30.5 (11.60)	20.5 (9.53)
Css	21.6 (9.17)	26.9 (12.4)	27.2 (10.5)	19.1 (9.11)

Control Cohort With Normal Renal and Normal Hepatic Function vs Mild Hepatic Impairment and Normal Renal Function (Mild HI): Geometric mean ratio: 1.30 (90% CI 0.95 to 1.78)
Control Cohort With Normal Renal and Normal Hepatic Function vs Moderate Hepatic Impairment and Normal Renal Function (Mod HI): Geometric mean ratio: 1.30 (90% CI 0.92 to 1.83)
Control Cohort With Normal Renal and Normal Hepatic Function vs Severe Hepatic Impairment and Normal Renal Function (Sev HI): Geometric mean ratio: 0.87 (90% CI 0.55 to 1.37)

Population analysed: Pharmacokinetic (PK) Population: A participant was considered evaluable for the PK analyses if he or she had a full profile of vismodegib samples

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

Time frame: Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8. Mean (Standard Deviation). Unit: Micromolar*hour

Measure	Control Cohort With Normal Renal and Normal Hepatic Function n = 9	Mild Hepatic Impairment and Normal Renal Function (Mild HI) n = 8	Moderate Hepatic Impairment and Normal Renal Function (Mod HI) n = 6	Severe Hepatic Impairment and Normal Renal Function (Sev HI) n = 3
Value	512 (222)	639 (304)	667 (274)	437 (197)

Control Cohort With Normal Renal and Normal Hepatic Function vs Mild Hepatic Impairment and Normal Renal Function (Mild HI): Geometric mean ratio: 1.24 (90% CI 0.89 to 1.73)
Control Cohort With Normal Renal and Normal Hepatic Function vs Moderate Hepatic Impairment and Normal Renal Function (Mod HI): Geometric mean ratio: 1.31 (90% CI 0.91 to 1.89)
Control Cohort With Normal Renal and Normal Hepatic Function vs Severe Hepatic Impairment and Normal Renal Function (Sev HI): Geometric mean ratio: 0.86 (90% CI 0.53 to 1.39)

Population analysed: Pharmacokinetic (PK) Population: A participant was considered evaluable for the PK analyses if he or she had a full profile of vismodegib samples

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 60 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control Cohort With Normal Renal and Normal Hepatic Function	3 of 9 (33.3%)	8 of 9 (88.9%)	Not reported
Mild Hepatic Impairment and Normal Renal Function (Mild HI)	4 of 8 (50%)	7 of 8 (87.5%)	Not reported
Moderate Hepatic Impairment and Normal Renal Function (Mod HI)	6 of 8 (75%)	8 of 8 (100%)	Not reported
Severe Hepatic Impairment and Normal Renal Function (Sev HI)	3 of 6 (50%)	6 of 6 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Genentech, Inc.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vismodegib in people with Cancer, run by Genentech, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib (time frame: Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01546519.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2016.