GlioblastomaPhase 1/2NCT02315534
A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma
A Phase 1/2 study testing BBI608 and Temozolomide in people with Glioblastoma, run by Sumitomo Pharma America, Inc. at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- BBI608 and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Mar 2015to 24 Jun 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Canada2 sites
University of Calgary
Calgary, Alberta
Princess Margaret Cancer Centre
Toronto, Ontario
United States1 site
Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
About this study
Official title: 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.
Read the 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.
- Conditions
- Glioblastoma
- Being tested
- BBI608, Temozolomide
- Keywords
- GBM, Malignant Glioma
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BBI608Drug
Also called Napabucasin, BB608, BBI-608
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.
TemozolomideDrug
Also called Temodar
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma. Receives: Drug: BBI608; Drug: Temozolomide |
| Arm B | Experimental | Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma. Receives: Drug: BBI608; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicities (DLTs)
Number of patients who experienced a dose limiting toxicity following a dosing of BBI608
Measured: 28 days after first administration of combination treatment (BBI608+TMZ)
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.
Measured: 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 outcomes (6)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 4 weeks
Overall Response Rate (ORR)
The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.
Measured: 4 weeks
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)
Measured: 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
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.
Measured: At the time of surgical resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2014 (estimated)
- Study startMar 2015
- Primary completion9 Oct 2018
- Study completion24 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumitomo Pharma America, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02315534
- Sponsor's protocol ID
- BBI608-251
- Other IDs
- BBI608-201GBM
- Status last verified
- Nov 2023
- First submitted
- 9 Dec 2014
- Last updated
- 15 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Clinical Study of BBI608 in Combination With Temozolomide for Adult Patients With Recurrent or Progressed Glioblastoma
- ClinicalTrials.gov ID
- NCT02315534
- Acronym / sponsor ID
- BBI608-251
- Conditions
- Glioblastoma
- Keywords
- GBM, Malignant Glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Sumitomo Pharma America, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2015
- Primary completion
- 9 Oct 2018 (actual)
- Study completion
- 24 Jun 2019 (actual)
- First posted
- 12 Dec 2014 (estimated)
- Results
- Posted 24 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: BBI608, Drug: TemozolomidePatients for whom surgery is recommended as part of treatment for recurrent Glioblastoma. |
| Arm B | Experimental | Drug: BBI608, Drug: TemozolomidePatients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BBI608Also: Napabucasin, BB608, BBI-608In 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. | Drug | Arm A, Arm B |
| TemozolomideAlso: TemodarTemozolomide (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. | Drug | Arm A, Arm B |
Primary outcome
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
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.
6 secondary outcomes
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
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.
Disease Control Rate (DCR)
Time frame: 4 weeks
Overall Response Rate (ORR)
Time frame: 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BBI608 and Temozolomide in people with Glioblastoma, run by Sumitomo Pharma America, Inc. at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicities (DLTs) (time frame: 28 days after first administration of combination treatment (BBI608+TMZ)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2023.