GDC-0449 in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT00980343|
Recruitment Status : Completed
First Posted : September 21, 2009
Results First Posted : August 16, 2017
Last Update Posted : August 16, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor||Drug: vismodegib Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis Other: pharmacological study||Phase 2|
I. 6-month progression-free survival (PFS-6) measured from start of treatment following surgery.
I. Toxicity. (Clinical) II. Overall survival. (Clinical) III. Tumor response. Partial Response (PR) + Complete Response (CR): MacDonald criteria). (Clinical)
- Determination of in vivo drug effect in recurrent Glioblastoma Multiform (GBM). (Correlative studies)
- Determination of in vitro drug effect on CD133+ glioma-derived neurospheres. (Correlative studies)
- Determination of Sonic Hedgehog pathway activation in primary vs. recurrent GBM. (Correlative studies)
I. Correlate clinical outcome (6 mo PFS) with biologic correlates (1-3) above.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive oral Hedgehog antagonist GDC-0449 once daily for 7 days before surgery.
Arm II: Patients do not receive treatment before surgery. Beginning within 28 days after surgical resection, all patients receive oral Hedgehog antagonist GDC-0449 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Fresh and paraffin-embedded tissue samples are collected for correlative laboratory studies.
After completion of study treatment, patients are followed up every 2 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Biomarker and Phase II Study of GDC-0449 in Patients With Recurrent Glioblastoma Multiforme|
|Study Start Date :||February 2010|
|Primary Completion Date :||May 2012|
|Study Completion Date :||June 2012|
Experimental: Arm I (pre-surgery vismodegib)
Patients receive oral Hedgehog antagonist GDC-0449 (vismodegib) once daily for 7 days before therapeutic conventional surgery. Beginning within 28 days after surgical resection, all patients receive oral Hedgehog antagonist GDC-0449 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis
Other Names:Procedure: therapeutic conventional surgery
undergo surgeryOther: laboratory biomarker analysis
correlative studiesOther: pharmacological study
Experimental: Arm II (no vismodegib pre-surgery)
Patients do not receive treatment before therapeutic conventional surgery.
Beginning within 28 days after surgical resection, all patients receive oral Hedgehog antagonist GDC-0449 (vismodegib) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Procedure: therapeutic conventional surgery
undergo surgeryOther: laboratory biomarker analysis
- 6 Months Progression-free Survival (PFS) [ Time Frame: 6 months ]Estimated using Kaplan Meier curves. six months calculated from date of treatment onset post-operatively. MRI scan at 6 months must be free of progression Progressive disease Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.
- Overall Survival Time [ Time Frame: 3 years ]The overall failure rate will be estimated along with 95% confidence intervals. A median time of survival will be estimated using standard methods.. Start date based on onset of treatment.
- Best Tumor Response Assessed by the Modified Macdonald Radiographic Response Criteria [ Time Frame: evaluated every 8 weeks - 1 year ]
The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features
1: complete response; 2: partial response; 3:stable disease; 4:progression
Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved
Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved
Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable
Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration
- Toxicity Incidence Grade 3 or 4 According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: 30 days from last dose of drug treatment - 1.5 years ]NCI CTCAE grade 3 or 4 possible, probable or definitely related events Grade 3 - severe Grade 4 - life threatening
- Incidence of CD133+ Neurospheres by Arm [ Time Frame: 12 hours post-vismodegib administration ]number of tumor-derived CD133 neurospheres undergoing proliferation and self-renewal
- Changes in Sonic Hedgehog Pathway Activation [ Time Frame: Pre-tumor resection and post tumor resection (12 hours) ]determined by Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) (Gli-1, Gli-2, PATCH (PTCH-1b)
- Determine Drug Effect (Pharmacokinetics) in Plasma for Arm 1 [ Time Frame: Day of surgery ]samples collected pre tumor resection (day of surgery) and post-tumor resection (day of surgery
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00980343
|United States, California|
|University of California at Los Angeles|
|Los Angeles, California, United States, 90095|
|University of California San Francisco|
|San Francisco, California, United States, 94115|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, North Carolina|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|University Hospitals Case Medical Center|
|Cleveland, Ohio, United States, 44106|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pennsylvania/Abramson Cancer Center|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Charles Nock, MD||National Cancer Institute (NCI)|