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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01209143
First received: September 23, 2010
Last updated: June 5, 2015
Last verified: June 2015

September 23, 2010
June 5, 2015
November 2010
March 2012   (final data collection date for primary outcome measure)
  • Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Rosiglitazone [ Time Frame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose ] [ Designated as safety issue: No ]
    On Days 1 and 8, blood samples were taken prior to the administration of rosiglitazone and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of rosiglitazone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma rosiglitazone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratio of AUC(0-inf) of rosiglitazone was defined as the AUC(0-inf) of rosiglitazone on Day 8/AUC(0-inf) of rosiglitazone on Day 1.
  • Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Rosiglitazone [ Time Frame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose ] [ Designated as safety issue: No ]
    On Days 1 and 8, blood samples were taken prior to the administration of rosiglitazone and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of rosiglitazone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma rosiglitazone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratio of Cmax of rosiglitazone was defined as the Cmax of rosiglitazone on Day 8/ Cmax of rosiglitazone on Day 1.
  • Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Ethinyl Estradiol and Norethindrone [ Time Frame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose ] [ Designated as safety issue: No ]
    On Days 1 and 8, blood samples were taken prior to the administration of the contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of ethinyl estradiol and norethindrone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma ethinyl estradiol and norethindrone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratios of AUC(0-inf) of ethinyl estradiol and norethindrone were defined as the ratios of AUC(0-inf) of ethinyl estradiol and norethindrone on Day 8 divided by AUC(0-inf) of ethinyl estradiol and norethindrone on Day 1, respectively.
  • Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone [ Time Frame: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose ] [ Designated as safety issue: No ]
    On Days 1 and 8, blood samples were taken prior to the administration of the contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of ethinyl estradiol and norethindrone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma ethinyl estradiol and norethindrone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratios of Cmax of ethinyl estradiol and norethindrone were defined as the ratios of Cmax of ethinyl estradiol and norethindrone on Day 8 divided by Cmax of ethinyl estradiol and norethindrone on Day 1, respectively.
  • 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 ]
Complete list of historical versions of study NCT01209143 on ClinicalTrials.gov Archive Site
Not Provided
  • 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 ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Cancers
  • Drug: Vismodegib
    Vismodegib was supplied in hard gelatin capsules.
    Other Name: GDC-0449
  • Drug: Rosiglitazone
    Rosiglitazone was supplied in tablets.
    Other Name: Rosiglitazone
  • Drug: Norethindrone/ethinyl estradiol
    Norethindrone/ethinyl estradiol was supplied in tablets.
  • Experimental: 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.
    Interventions:
    • Drug: Vismodegib
    • Drug: Rosiglitazone
  • Experimental: 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.
    Interventions:
    • Drug: Vismodegib
    • Drug: Norethindrone/ethinyl estradiol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
March 2012
March 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01209143
SHH4593g, GO01353
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Dawn Colburn, Pharm.D. Genentech, Inc.
Genentech, Inc.
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP