Evaluation of Food Effect on Pharmacokinetics of Vismodegib

NCT01174264 | Completed Phase 1 Results

• 6 other identifiers: NCI-2012-03099NCI 839509-149-B8395P30CA014599U01CA069852
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Neoplasm

Outcome Measures

Primary Outcomes (8)

• 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.

  168 hours

• AUC Following Single Dose of Drug

  Area under the curve from 0-168 hours.

  168 hours

• Tmax'Following Single Dose of Drug

  Time of maximum drug concentration

  168 hours

• Tlag Following Single Dose of Drug

  Time between drug administration and when it is first observed in the systemic circulation.

  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.

  24 hours

• Cmax Following Steady State Exposure for 14 Days

  Maximum drug concentration over 24 hours.

  24 hours

• AUC Following Steady State Exposure for 14 Days

  Area under the curve from 0 to 24 hours.

  24 hours

• Tmax Following Steady State Exposure for 14 Days

  Time of maximum drug concentration.

  24 hours

Secondary Outcomes (1)

• Objective Responses in Patients With Solid Tumors

  Up to 30 days

Study Arms (3)

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.

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.

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.

Other: Pharmacological Study; Drug: Vismodegib

Interventions

Pharmacological Study OTHER

Correlative studies

Arm I (vismodegib on empty stomach); Arm II (vismodegib after high fat meal); Arm III (vismodegib after low fat meal)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

Arm I (vismodegib on empty stomach); Arm II (vismodegib after high fat meal); Arm III (vismodegib after low fat meal)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

HhAntag691

Results Point of Contact

• Title: Theodore Karrison
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

773-702-9326

Study Officials

• Manish Sharma

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2010
• First Posted: August 3, 2010
• Study Start: October 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 19, 2017
• Results First Posted: March 15, 2016

Record last verified: 2017-04

Locations

US (1)