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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Solid Cancers	Drug: GDC-0449 Drug: oral contraceptive Drug: rosiglitazone	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Drug Reactions

Drug Information available for: Rosiglitazone Rosiglitazone Maleate Vismodegib

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

To evaluate the relative effect of GDC-0449 on the pharmacokinetics (Cmax and AUC) of oral contraceptive (OC; norethindrone and ethinyl estradiol) [ Time Frame: Days 1-9 ] [ Designated as safety issue: No ]
To evaluate the relative effect of GDC-0449 on the pharmacokinetics (Cmax and AUC) of rosiglitazone [ Time Frame: Days 1-9 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The safety objective of this study is to evaluate the safety and tolerability of GDC-0449 administered to patients with advanced solid tumors that are refractory to treatment or for whom no standard therapy exists [ Time Frame: 63 days, then every 4 weeks while patient is on study ] [ Designated as safety issue: No ]
The secondary efficacy objective of this study is to make a preliminary assessment of tumor response in patients with advanced solid tumors who are refractory to treatment or for whom no standard therapy exists receiving GDC-0449 [ Time Frame: 63 days, then every 8 weeks while patient is on study ] [ Designated as safety issue: No ]

Enrollment:	53
Study Start Date:	November 2010
Study Completion Date:	July 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1	Drug: GDC-0449 Oral repeating dose Drug: rosiglitazone Oral repeating dose
Experimental: Cohort 2	Drug: GDC-0449 Oral repeating dose Drug: oral contraceptive Oral repeating dose

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01209143

Locations

United States, California

Stanford, California, United States, 94305
United States, Michigan

Detroit, Michigan, United States, 48201
United States, Texas

Houston, Texas, United States, 77030

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Dawn Colburn, Pharm.D.

Genentech

More Information

No publications provided

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT01209143 History of Changes
Other Study ID Numbers:	SHH4593g, GO01353
Study First Received:	September 23, 2010
Last Updated:	December 21, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Contraceptive Agents
Contraceptives, Oral
Contraceptives, Oral, Combined
Rosiglitazone
Reproductive Control Agents

Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Hypoglycemic Agents

ClinicalTrials.gov processed this record on May 22, 2013