Solid CancersPhase 1NCT01209143
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 1 study testing Vismodegib, Rosiglitazone and Norethindrone/ethinyl estradiol in people with Solid Cancers, run by Genentech, Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Cancers
- What is being tested?
- Vismodegib, Rosiglitazone and Norethindrone/ethinyl estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2010to Mar 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Study site
Detroit, Michigan, 48201
Study site
Houston, Texas, 77030
Study site
Stanford, California, 94305
About this study
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
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
- Being tested
- Vismodegib, Rosiglitazone, Norethindrone/ethinyl estradiol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VismodegibDrug
Also called GDC-0449
Vismodegib was supplied in hard gelatin capsules.
RosiglitazoneDrug
Rosiglitazone was supplied in tablets.
Norethindrone/ethinyl estradiolDrug
Norethindrone/ethinyl estradiol was supplied in tablets.
| Study group | Role | What they receive |
|---|---|---|
| Vismodegib + rosiglitazone | Experimental | 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. Receives: Drug: Vismodegib; Drug: Rosiglitazone |
| Vismodegib + oral contraceptive | Experimental | 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. Receives: Drug: Vismodegib; Drug: Norethindrone/ethinyl estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Rosiglitazone
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.
Measured: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Rosiglitazone
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.
Measured: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Ethinyl Estradiol and Norethindrone
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.
Measured: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
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.
Measured: Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2010 (estimated)
- Study startNov 2010
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid CancersStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dawn Colburn, Pharm.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01209143
- Sponsor's protocol ID
- SHH4593g
- Other IDs
- GO01353
- Status last verified
- Jun 2015
- First submitted
- 23 Sep 2010
- Last updated
- 29 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01209143
- Acronym / sponsor ID
- SHH4593g
- Conditions
- Solid Cancers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 27 Sep 2010 (estimated)
- Results
- Posted 29 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vismodegib + rosiglitazone | Experimental | Drug: Vismodegib, Drug: RosiglitazoneParticipants 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. |
| Vismodegib + oral contraceptive | Experimental | Drug: Vismodegib, Drug: Norethindrone/ethinyl estradiolParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VismodegibAlso: GDC-0449Vismodegib was supplied in hard gelatin capsules. | Drug | Vismodegib + oral contraceptive, Vismodegib + rosiglitazone |
| RosiglitazoneRosiglitazone was supplied in tablets. | Drug | Vismodegib + rosiglitazone |
| Norethindrone/ethinyl estradiolNorethindrone/ethinyl estradiol was supplied in tablets. | Drug | Vismodegib + oral contraceptive |
Primary outcome
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
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
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
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
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dawn Colburn, Pharm.D. study director
Genentech, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vismodegib, Rosiglitazone and Norethindrone/ethinyl estradiol in people with Solid Cancers, run by Genentech, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2015.