Malignant NeoplasmPhase 1/2NCT01174264
Evaluation of Food Effect on Pharmacokinetics of Vismodegib
A Phase 1/2 study testing Pharmacological Study and Vismodegib in people with Malignant Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized clinical trial studies the effect of food on the pharmacokinetics of vismodegib. Studying the effects of meals on the absorption of vismodegib may help doctors prescribe correct doses and label the drug accurately. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Malignant Neoplasm
- What is being tested?
- Pharmacological Study and Vismodegib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Dec 2014
- Phase
- Phase 1/2
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed advanced malignancies (except for leukemias) refractory to standard of care therapy, or for whom no standard of care therapy is available
- Measurable or non-measurable disease
- An anticipated life expectancy > 3 months
- Karnofsky performance status of > 70%
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
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- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine =< 1.5 X institutional upper limit of normal
- Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 48 hours prior to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449
- Female subjects of childbearing potential are defined as follows:
- Patients with regular menses
- Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
- Women who have had tubal ligation
- Female subjects may be considered to NOT be of childbearing potential for the following reasons:
- The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy
- The patient is medically confirmed to menopausal (no menstrual period) for 24 consecutive months
- Pre-pubertal females; the parent or guardian of young female patients who have not yet started menstruation should verify that menstruation has not begun; if a young female patient reaches menarche during the study, then she is to be considered as a woman of childbearing potential from that time forward
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in study
- Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
- Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis are ineligible
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- Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GDC-0449
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients with medical conditions that require the following medications will be excluded
- Strong inhibitors of cytochrome P450 3A4 (CYP3A4) (clarithromycin, itraconazole, ketoconazole, nefazodone, erythromycin, grapefruit juice, verapamil, and diltiazem)
- Strong inhibitors of cytochrome P450 2C9 (CYP2C9) (fluconazole and amiodarone)
- Inducers of CYP3A4 (carbamazepine, dexamethasone, modafinil, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, troglitazone)
- Inducers of CYP2C9 (rifampin, and secobarbital)
- Patients who have a medical condition or dietary restrictions that prevent him or her from fasting for at least 10 hours (overnight) or eating a high calorie meal
- Any ambiguity in the inclusion/exclusion criteria should be clarified and resolved by communication with the study investigators
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
About this study
Official title: Evaluation of Food Effect on Pharmacokinetics of GDC-0449, an Inhibitor of Hedgehog Signaling
This randomized clinical trial studies the effect of food on the pharmacokinetics of vismodegib. Studying the effects of meals on the absorption of vismodegib may help doctors prescribe correct doses and label the drug accurately.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the effect of prandial states on the pharmacokinetic parameters of GDC-0449 (vismodegib).
II. To evaluate the effect of fat content of meals on the pharmacokinetic parameters of GDC-0449.
SECONDARY OBJECTIVES:
- To evaluate the effect of prandial states and fat content of meals on the safety profile of GDC-0449.
II. To describe any anticancer activities of GDC-0449.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive a single dose of vismodegib orally (PO) on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
ARM II: Patients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
ARM III: Patients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28.
In all arms, treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Malignant Neoplasm
- Being tested
- Pharmacological Study, Vismodegib
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Correlative studies
VismodegibDrug
Also called Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (vismodegib on empty stomach) | Experimental | Patients receive a single dose of vismodegib PO on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28. Receives: Other: Pharmacological Study; Drug: Vismodegib |
| Arm II (vismodegib after high fat meal) | Experimental | Patients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28. Receives: Other: Pharmacological Study; Drug: Vismodegib |
| Arm III (vismodegib after low fat meal) | Experimental | Patients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28. Receives: Other: Pharmacological Study; Drug: Vismodegib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax Following Single Dose of Drug
Highest observed concentration over the 168 hour period. Blood samples were collected at j0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 24, 48, 120, and 168 hours.
Measured: 168 hours
AUC Following Single Dose of Drug
Area under the curve from 0-168 hours.
Measured: 168 hours
Tmax'Following Single Dose of Drug
Time of maximum drug concentration
Measured: 168 hours
Tlag Following Single Dose of Drug
Time between drug administration and when it is first observed in the systemic circulation.
Measured: 168 hours
Ctrough Following Steady State Exposure for 14 Days
Minimum blood concentration over 24-hour observation period. Blood sample collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 24 hours.
Measured: 24 hours
Cmax Following Steady State Exposure for 14 Days
Maximum drug concentration over 24 hours.
Measured: 24 hours
AUC Following Steady State Exposure for 14 Days
Area under the curve from 0 to 24 hours.
Measured: 24 hours
Tmax Following Steady State Exposure for 14 Days
Time of maximum drug concentration.
Measured: 24 hours
Secondary outcomes (1)
Objective Responses in Patients With Solid Tumors
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2010 (estimated)
- Study startOct 2009
- Primary completionDec 2014
- Study completionDec 2014
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 Malignant NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Manish Sharma, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01174264
- Sponsor's protocol ID
- NCI-2012-03099
- Other IDs
- NCI-2012-03099, NCI 8395, 09-149-B, 8395, P30CA014599, U01CA069852
- Status last verified
- Apr 2017
- First submitted
- 30 Jul 2010
- Last updated
- 19 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Food Effect on Pharmacokinetics of GDC-0449, an Inhibitor of Hedgehog Signaling
- ClinicalTrials.gov ID
- NCT01174264
- Acronym / sponsor ID
- NCI-2012-03099
- Conditions
- Malignant Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 3 Aug 2010 (estimated)
- Results
- Posted 15 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized clinical trial studies the effect of food on the pharmacokinetics of vismodegib. Studying the effects of meals on the absorption of vismodegib may help doctors prescribe correct doses and label the drug accurately.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the effect of prandial states on the pharmacokinetic parameters of GDC-0449 (vismodegib).
II. To evaluate the effect of fat content of meals on the pharmacokinetic parameters of GDC-0449.
SECONDARY OBJECTIVES:
- To evaluate the effect of prandial states and fat content of meals on the safety profile of GDC-0449.
II. To describe any anticancer activities of GDC-0449.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive a single dose of vismodegib orally (PO) on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
ARM II: Patients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28.
ARM III: Patients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28.
In all arms, treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I (vismodegib on empty stomach) | Experimental | Other: Pharmacological Study, Drug: VismodegibPatients receive a single dose of vismodegib PO on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28. |
| Arm II (vismodegib after high fat meal) | Experimental | Other: Pharmacological Study, Drug: VismodegibPatients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28. |
| Arm III (vismodegib after low fat meal) | Experimental | Other: Pharmacological Study, Drug: VismodegibPatients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically confirmed advanced malignancies (except for leukemias) refractory to standard of care therapy, or for whom no standard of care therapy is available
- Measurable or non-measurable disease
- An anticipated life expectancy > 3 months
- Karnofsky performance status of > 70%
- Leukocytes >= 3,000/mcL
Key exclusion criteria (17 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in study
- Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
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 |
|---|---|---|
| Pharmacological StudyCorrelative studies | Other | Arm I (vismodegib on empty stomach), Arm II (vismodegib after high fat meal), Arm III (vismodegib after low fat meal) |
| VismodegibAlso: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449Given PO | Drug | Arm I (vismodegib on empty stomach), Arm II (vismodegib after high fat meal), Arm III (vismodegib after low fat meal) |
Primary outcome
Cmax Following Single Dose of Drug
Time frame: 168 hours
Highest observed concentration over the 168 hour period. Blood samples were collected at j0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 24, 48, 120, and 168 hours.
AUC Following Single Dose of Drug
Time frame: 168 hours
Area under the curve from 0-168 hours.
Tmax'Following Single Dose of Drug
Time frame: 168 hours
Time of maximum drug concentration
Tlag Following Single Dose of Drug
Time frame: 168 hours
Time between drug administration and when it is first observed in the systemic circulation.
Ctrough Following Steady State Exposure for 14 Days
Time frame: 24 hours
Minimum blood concentration over 24-hour observation period. Blood sample collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 24 hours.
Cmax Following Steady State Exposure for 14 Days
Time frame: 24 hours
Maximum drug concentration over 24 hours.
AUC Following Steady State Exposure for 14 Days
Time frame: 24 hours
Area under the curve from 0 to 24 hours.
Tmax Following Steady State Exposure for 14 Days
Time frame: 24 hours
Time of maximum drug concentration.
1 secondary outcome
Objective Responses in Patients With Solid Tumors
Time frame: Up to 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2017.
- 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.
Manish Sharma principal investigator
University of Chicago Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pharmacological Study and Vismodegib in people with Malignant Neoplasm, run by National Cancer Institute (NCI) at 1 site 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 21 inclusion and 17 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 19 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 15 Mar 2016). 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?
Cmax Following Single Dose of Drug (time frame: 168 hours). The study lists 8 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 19 May 2017; AzTrials last refreshed its copy on 8 Nov 2026.