Clinical trial NCT01209143: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-27
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Rosiglitazone
timeFrame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
measure: Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Rosiglitazone
timeFrame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
measure: Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Ethinyl Estradiol and Norethindrone
timeFrame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
measure: Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
timeFrame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
state: California
city: Detroit
country: United States
state: Michigan
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Genentech, Inc.
name: Dawn Colburn, Pharm.D.
role: STUDY_DIRECTOR
References: