Back to resultsA Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma
Primary Purpose
Glioblastoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BBI608
Temozolomide
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring GBM, Malignant Glioma
Eligibility Criteria
Major Eligibility Criteria
- Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements.
- A histologically confirmed supratentorial glioblastoma (GBM) at first recurrence/progression (except for transformation from previous low grade glioma) following standard front-line therapy, for which treatment with temozolomide (TMZ) would be acceptable as determined by the Investigator
- Previously received standard front-line GBM treatment including maximal surgical resection followed by external beam radiation therapy.
- Patients may or may not be candidates for repeat surgical resection of the recurrent/progressed GBM.
- Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a minimum of 12 weeks following completion of chemoradiation or radiation therapy.
- Patients must have measurable or non-measurable disease by response assessment in neuro-oncology Response Assessment in Neuro-oncology (RANO) criteria
Sites / Locations
- Laura and Isaac Perlmutter Cancer Center
- University of Calgary
- Princess Margaret Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A
Arm B
Arm Description
Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.
Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.
Outcomes
Primary Outcome Measures
Dose-limiting Toxicities (DLTs)
Number of patients who experienced a dose limiting toxicity following a dosing of BBI608
Progression Free Survival (PFS)-6
To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment.
Secondary Outcome Measures
Progression Free Survival (PFS)-12
To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment.
Overall Survival (OS)
To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection.
Disease Control Rate (DCR)
To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline.
Overall Response Rate (ORR)
The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.
Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve
The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method)
Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors
Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.
Full Information
NCT ID
NCT02315534
First Posted
December 9, 2014
Last Updated
April 4, 2022
Sponsor
Sumitomo Pharma America, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02315534
Brief Title
A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma
Official Title
A Phase Ib/II Clinical Study of BBI608 in Combination With Temozolomide for Adult Patients With Recurrent or Progressed Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
October 9, 2018 (Actual)
Study Completion Date
June 24, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sumitomo Pharma America, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open label, multi-center, phase 1 safety run-in and phase 2 study of BBI608 in combination with temozolomide in patients with recurrent or progressive glioblastoma who have not received prior bevacizumab therapy.
Detailed Description
In arm A, patients who are candidates for surgical resection will receive BBI608 as monotherapy prior to resection, followed by post-operative BBI608 administered in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, in combination with temozolomide.
In the phase 1/dose-limiting toxicity (DLT) cohort portion of this study, pharmacokinetics will be evaluated for both arms A and B. Pharmacodynamics will be evaluated in all patients who undergo surgical resection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
GBM, Malignant Glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.
Intervention Type
Drug
Intervention Name(s)
BBI608
Other Intervention Name(s)
Napabucasin, BB608, BBI-608
Intervention Description
In arm A, BBI608 will be administered at the recommended Phase 2 dose (RP2D) twice daily for 7(±2) days prior to planned surgical resection or biopsy of recurrent GBM. Upon the clinical recovery of the patient and at a time between 15-28 days after surgery, BBI608 will be administered orally, daily, each day of a 28 day cycle in combination with temozolomide.
In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, each day of a 28 day cycle at the RP2D in combination with temozolomide.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar
Intervention Description
Temozolomide (TMZ) will be administered orally, once daily, at a dose of 150 mg/m^2 daily on days 1 through 5 of each 28-day study cycle. The dose of temozolomide can be increased to 200 mg/m^2 as per standard TMZ dosing guidelines for patients who complete at least one cycle at 150 mg/m^2.
Primary Outcome Measure Information:
Title
Dose-limiting Toxicities (DLTs)
Description
Number of patients who experienced a dose limiting toxicity following a dosing of BBI608
Time Frame
28 days after first administration of combination treatment (BBI608+TMZ)
Title
Progression Free Survival (PFS)-6
Description
To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment.
Time Frame
From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)-12
Description
To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment.
Time Frame
From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months
Title
Overall Survival (OS)
Description
To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection.
Time Frame
From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death.
Title
Disease Control Rate (DCR)
Description
To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline.
Time Frame
4 weeks
Title
Overall Response Rate (ORR)
Description
The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.
Time Frame
4 weeks
Title
Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve
Description
The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method)
Time Frame
On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608
Title
Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors
Description
Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.
Time Frame
At the time of surgical resection
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Major Eligibility Criteria
Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements.
A histologically confirmed supratentorial glioblastoma (GBM) at first recurrence/progression (except for transformation from previous low grade glioma) following standard front-line therapy, for which treatment with temozolomide (TMZ) would be acceptable as determined by the Investigator
Previously received standard front-line GBM treatment including maximal surgical resection followed by external beam radiation therapy.
Patients may or may not be candidates for repeat surgical resection of the recurrent/progressed GBM.
Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a minimum of 12 weeks following completion of chemoradiation or radiation therapy.
Patients must have measurable or non-measurable disease by response assessment in neuro-oncology Response Assessment in Neuro-oncology (RANO) criteria
Facility Information:
Facility Name
Laura and Isaac Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma
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