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

Sumitomo Pharma America, Inc.34 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma

Interventions

BBI608DRUG

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

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Laura and Isaac Perlmutter Cancer Center

New York, New York, United States

University of Calgary

Calgary, Alberta, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Dose-limiting Toxicities (DLTs)

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)

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.

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 Outcomes

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.

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)

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.

Data from ClinicalTrials.gov

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