Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma
|Adult Brain Glioblastoma||Other: Laboratory Biomarker Analysis Drug: Methoxyamine Drug: Temozolomide||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase II Study of TRC102 in Combination With Temozolomide for Recurrent Glioblastoma|
- Objective response as assessed by Response Assessment in Neuro-Oncology (RANO) criteria (Arm I) [ Time Frame: Up to at least 2 years ]To test the hypothesis that the combination treatment of temozolomide and methoxyamine will achieve 30% radiographic response rate (partial response + complete response) in patients with first recurrence of glioblastoma.
- Objective response rate (PR+CR) as assessed by RANO criteria (Arm II) [ Time Frame: Up to at least 2 years ]
- Incidence toxicity graded according to the National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 30 days following the last dose of study drug ]Will be analyzed using standard descriptive statistical methods.
- Overall survival [ Time Frame: Up to at least 2 years ]Will be analyzed using standard descriptive statistical methods.
- Progression-free survival [ Time Frame: Up to at least 2 years ]Will be analyzed using standard descriptive statistical methods.
- Progression-free survival at 6 months [ Time Frame: 6 months ]Will be analyzed using standard descriptive statistical methods.
- MPG, topo II-alpha, and MGMT levels in tissue samples [ Time Frame: Baseline ]MPG, topo II-alpha, and MGMT levels will be correlated with response, PFS, and overall survival. Will be analyzed using standard descriptive statistical methods.
|Actual Study Start Date:||December 18, 2015|
|Estimated Primary Completion Date:||August 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (methoxyamine, temozolomide)
Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Methoxyamine
Other Name: TRC102Drug: Temozolomide
I. To estimate the efficacy of TRC102 (methoxyamine) and temozolomide, as measured by response rate, in bevacizumab naïve glioblastoma. (Arm I) II. To estimate the efficacy of TRC102 and temozolomide, as measured by response rate, in bevacizumab refractory glioblastoma. (Arm II)
I. Evaluate the toxicities of oral TRC102 and temozolomide in this patient population.
II. Estimate the efficacy of TRC102 and temozolomide, as measured by progression-free survival, progression-free survival at 6 months and overall survival, in bevacizumab naïve glioblastoma.
III. Estimate the efficacy of TRC102 and temozolomide, as measured by progression-free survival in bevacizumab refractory glioblastoma.
I. Assess the tissue correlates of N-methylpurine-deoxyribonucleic acid (DNA) glycosylase (MPG), topoisomerase II-alpha (topo II a), and O-6-methylguanine-DNA methyltransferase (MGMT) status, with response, progression-free survival (PFS), and overall survival.
Patients receive methoxyamine orally (PO) once daily (QD) and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, and then every 6 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02395692
|United States, Alabama|
|University of Alabama at Birmingham Cancer Center|
|Birmingham, Alabama, United States, 35233|
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|UCSF Medical Center-Parnassus|
|San Francisco, California, United States, 94143|
|United States, Maryland|
|Adult Brain Tumor Consortium|
|Baltimore, Maryland, United States, 21231-1000|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|Henry Ford Cancer Institute¿Downriver|
|Brownstown Charter Township, Michigan, United States, 48183|
|Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|Henry Ford West Bloomfield Hospital|
|West Bloomfield Township, Michigan, United States, 48322|
|United States, North Carolina|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Manmeet Ahluwalia||National Cancer Institute (NCI)|