Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
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|ClinicalTrials.gov Identifier: NCT03250299|
Recruitment Status : Active, not recruiting
First Posted : August 15, 2017
Last Update Posted : July 1, 2022
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma MGMT-Unmethylated Glioblastoma||Drug: Microtubule-Targeted Agent BAL101553 Radiation: Radiation Therapy Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
I. To determine the maximum tolerated dose of microtubule-targeted agent BAL101553 (BAL101553) in combination with standard radiation in patients with newly diagnosed MGMT promoter unmethylated glioblastoma (GBM).
I. To estimate safety and tolerability of the combination of BAL101553 in combination with standard radiation in patients with newly diagnosed MGMT promoter unmethylated GBM.
II. To determine overall and progression-free survival. III. To assess the pharmacokinetics of BAL101553 and BAL27862. IV. To explore expression of biomarkers, including BubR1, stathmin and EB1 at baseline (exploratory biomarkers).
OUTLINE: This is a dose escalation study of the microtubule-targeted agent BAL101553.
Patients receive microtubule-targeted agent BAL101553 orally (PO) once daily (QD) on days 1-42 and undergo concomitant standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, and then every 2 months for 2 years and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study to Determine the Safety and Tolerability of the Oral Microtubule Destabilizer BAL101553 in Combination With Standard Radiation in Patients With MGMT Promoter Unmethylated Newly Diagnosed Glioblastoma|
|Actual Study Start Date :||June 7, 2017|
|Actual Primary Completion Date :||June 6, 2022|
|Estimated Study Completion Date :||August 2022|
Experimental: Dose Finding
Fixed 3+3 dose escalation of BAL101553 (7 days per week), combined with RT days 1-5 for 6 weeks followed by 4 week rest.
Drug: Microtubule-Targeted Agent BAL101553
Other Name: BAL101553, Microtubule-targeted Agent BAL101553
Radiation: Radiation Therapy
Undergo radiation therapy
Other Name: Cancer Radiotherapy, Irradiate, irradiated, irradiation, RADIATION, Radiation, radiation therapy, Radiation Therapy, Radiotherapeutics, radiotherapy, Radiotherapy, RT, Therapy, Radiation
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum Tolerated Dose (MTD) [ Time Frame: up to 10 weeks ]Number of Dose limited Toxicities per dose level. ANC < 500/mm3; Platelets < 25K; Febrile neutropenia; any event which prevents 80% administration of planned BAL101553 dose; >/= gr 2 CNS ischemia; >/= gr 2 neurological toxicities interfering with AODL not resolved within 2wks; gr 3/4 non-hematological, non-CNS toxicities with expections
- Proportion of subjects with Grade 3 and Grade 4 AEs [ Time Frame: up to 10 weeks ]CTC AE 4.0 / 5.0
- Overall Survival [ Time Frame: initial diagnosis to date of death - up to 2 years ]Median time of survival along with 95% confidence interval
- Progression Free Survival [ Time Frame: initial diagnosis to date of progression - up to 2 years ]Median time of progression-free survival along with 95% confidence interval
- Maximum Plasma Concentration [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22 ]PK of microtubule-targeted agent BAL101553 and BAL27862
- Time of Maximum Plasma Concentraion [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22 ]PK of microtubule-targeted agent BAL101553 and BAL27862
- Area Under the Concentration-time Curve (AUC) [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22 ]PK of microtubule-targeted agent BAL101553 and BAL27862
- Half-life [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22 ]PK of microtubule-targeted agent BAL101553 and BAL27862
- Clearance and Volume [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22 ]PK of microtubule-targeted agent BAL101553 and BAL27862
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): NCT03250299
|United States, Alabama|
|UAB Comprehensive Cancer Center|
|Birmingham, Alabama, United States, 35294-3410|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21205|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at 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 Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|Abrams Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Hillman Cancer Center at University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15232|
|Study Chair:||Matthias Holdhoff, MD||National Cancer Institute (NCI)|