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

NCT02315534 | Completed Phase 1 Results

• 2 other identifiers: BBI608-251BBI608-201GBM
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 3

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.

Conditions

Glioblastoma

Keywords

GBM; Malignant Glioma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicities (DLTs)

  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

  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 Outcomes (6)

• Progression Free Survival (PFS)-12

  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)

  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)

  4 weeks

• Overall Response Rate (ORR)

  4 weeks

• Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve

  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

Study Arms (2)

Arm A

EXPERIMENTAL

Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.

Drug: BBI608; Drug: Temozolomide

Arm B

EXPERIMENTAL

Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.

Drug: BBI608; Drug: Temozolomide

Interventions

BBI608 DRUG

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.

Also known as: Napabucasin, BB608, BBI-608

Arm A; Arm B

Temozolomide DRUG

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.

Also known as: Temodar

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (3)

Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

University of Calgary

Calgary, Alberta, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

napabucasin; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Connor Marshall
• Organization: Sumitomo Dainippon Pharma Oncology

cmarshall@bostonbiomedical.com

843-364-8039

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: December 12, 2014
• Study Start: March 1, 2015
• Primary Completion: October 9, 2018
• Study Completion: June 24, 2019
• Last Updated: November 15, 2023
• Results First Posted: September 24, 2021

Record last verified: 2023-11

Locations

US (1); CA (2)