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

Condition(s) targeted: Solid Cancers

Intervention: Vismodegib (Drug); Rosiglitazone (Drug); Norethindrone/ethinyl estradiol (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Genentech, Inc.

Official(s) and/or principal investigator(s):
Dawn Colburn, Pharm.D., Study Director, Affiliation: Genentech, Inc.

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.

Official title: A Phase Ib, Open-Label, 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

Study design: Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Rosiglitazone

Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Rosiglitazone

Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Ethinyl Estradiol and Norethindrone

Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Stanford, California 94305, United States

Detroit, Michigan 48201, United States

Houston, Texas 77030, United States

Starting date: November 2010
Last updated: June 5, 2015