GDC-0449 in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
|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|
|Actual Primary Completion Date :||May 2012|
|Actual 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
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)|