A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma

November 13, 2023 updated by: Sumitomo Pharma America, Inc.

A Phase Ib/II Clinical Study of BBI608 in Combination With Temozolomide for Adult Patients With Recurrent or Progressed Glioblastoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • University of Calgary
    • Ontario
      • Toronto, Ontario, Canada
        • Princess Margaret Cancer Centre
  • United States
    • New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Major Eligibility Criteria

  1. Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements.
  2. 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
  3. Previously received standard front-line GBM treatment including maximal surgical resection followed by external beam radiation therapy.
  4. Patients may or may not be candidates for repeat surgical resection of the recurrent/progressed GBM.
  5. Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a minimum of 12 weeks following completion of chemoradiation or radiation therapy.
  6. Patients must have measurable or non-measurable disease by response assessment in neuro-oncology Response Assessment in Neuro-oncology (RANO) criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.
Drug: BBI608

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.

Other Names:
  • Napabucasin
  • BBI-608
  • BB608
Drug: Temozolomide
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.
Other Names:
  • Temodar
Experimental: Arm B
Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.
Drug: BBI608

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.

Other Names:
  • Napabucasin
  • BBI-608
  • BB608
Drug: Temozolomide
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.
Other Names:
  • Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting Toxicities (DLTs)
Time Frame: 28 days after first administration of combination treatment (BBI608+TMZ)
Number of patients who experienced a dose limiting toxicity following a dosing of BBI608
28 days after first administration of combination treatment (BBI608+TMZ)
Progression Free Survival (PFS)-6
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
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.
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 Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)-12
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
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.
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
Overall Survival (OS)
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.
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.
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.
Disease Control Rate (DCR)
Time Frame: 4 weeks
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.
4 weeks
Overall Response Rate (ORR)
Time Frame: 4 weeks
The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.
4 weeks
Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve
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
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)
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
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
Time Frame: At the time of surgical resection
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.
At the time of surgical resection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sumitomo Pharma America, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

October 9, 2018

Study Completion (Actual)

June 24, 2019

Study Registration Dates

First Submitted

December 9, 2014

First Submitted That Met QC Criteria

December 9, 2014

First Posted (Estimated)

December 12, 2014

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 13, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBI608-251
  • BBI608-201GBM (Other Identifier: Boston Biomedical, Inc.)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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