A Study of Pharmacokinetic Drug Interaction Study of the Hedgehog Pathway Inhibitor GDC-0449 in Combination With Rosiglitazone or Combined Oral Contraceptive in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists

NCT ID: NCT01209143

Last Updated: 2015-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2012-03-31

Brief Summary

This is a single-arm, multicenter, Phase Ib study designed to describe the effect of GDC-0449 on the pharmacokinetics of rosiglitazone and oral contraceptives in patients with advanced solid tumors who are refractory to treatment or for whom no standard therapy exists.

Conditions

Solid Cancers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vismodegib + rosiglitazone

Participants received rosiglitazone 4 mg orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Group Type: EXPERIMENTAL

Vismodegib

Intervention Type: DRUG

Vismodegib was supplied in hard gelatin capsules.

Rosiglitazone

Intervention Type: DRUG

Rosiglitazone was supplied in tablets.

Vismodegib + oral contraceptive

Participants received the oral contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Group Type: EXPERIMENTAL

Vismodegib

Intervention Type: DRUG

Vismodegib was supplied in hard gelatin capsules.

Norethindrone/ethinyl estradiol

Intervention Type: DRUG

Norethindrone/ethinyl estradiol was supplied in tablets.

Interventions

Vismodegib

Vismodegib was supplied in hard gelatin capsules.

Intervention Type: DRUG

Rosiglitazone

Rosiglitazone was supplied in tablets.

Intervention Type: DRUG

Norethindrone/ethinyl estradiol

Norethindrone/ethinyl estradiol was supplied in tablets.

Intervention Type: DRUG

Other Intervention Names

GDC-0449

Eligibility Criteria

Inclusion Criteria

• Histologic documentation of incurable, locally advanced, or metastatic solid malignancy that has failed to respond to at least one prior regimen or for which there is no standard therapy
• Documented negative serum pregnancy test for women of childbearing potential and use of two forms of contraception. Contraception must be used while the patient is enrolled in the study and for 12 months after the patient discontinues from the study.
• For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 3 months after their last dose of GDC-0449.
• Agreement not to donate blood or blood products during the study and for at least 12 months after their last dose of GDC-0449
• For male patients, agreement not to donate sperm during the study and for at least 3 months after their last dose of GDC-0449
• Adequate hematopoietic capacity
• Adequate renal function
• Adequate hepatic function
• At least 3 weeks since the patient's last chemotherapy, investigational agent, radiation therapy, or major surgical procedure and recovery to pre-treatment baseline or stabilization of all treatment-related toxicities

Exclusion Criteria

• Active infection requiring intravenous (IV) antibiotics
• Clinically important history of liver disease significantly impairing hepatic function, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
• Any medical condition or diagnosis that would likely impair absorption of an orally administered drug
• Pregnant or lactating
• Treatment with excluded medications, including strong CYP450 inhibitors and inducers, within 2 weeks of study entry
• Male patients already receiving rosiglitazone
• Male patients with a known contraindication to rosiglitazone
• Female patients already receiving oral contraception < 14 days prior to Day 1
• Female patients with known contraindication to oral contraceptions

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dawn Colburn, Pharm.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Stanford, California, United States

Detroit, Michigan, United States

Houston, Texas, United States

Countries

United States

Other Identifiers

GO01353

Identifier Type: OTHER

Identifier Source: secondary_id

SHH4593g

Identifier Type: -

Identifier Source: org_study_id