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

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ClinicalTrials.gov Identifier: NCT02315534
Recruitment Status : Completed
First Posted : December 12, 2014
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Boston Biomedical, Inc

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: BBI608 Drug: Temozolomide Phase 1 Phase 2

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/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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Clinical Study of BBI608 in Combination With Temozolomide for Adult Patients With Recurrent or Progressed Glioblastoma
Study Start Date : March 2015
Actual Primary Completion Date : October 9, 2018
Actual Study Completion Date : October 9, 2018

Resource links provided by the National Library of Medicine


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 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
  • BB608
  • BBI-608

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 Name: 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 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
  • BB608
  • BBI-608

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 Name: Temodar




Primary Outcome Measures :
  1. Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) (Phase 1 portion) [ Time Frame: 4 weeks ]
  2. Progression Free Survival (PFS)-6 (phase 2 portion) [ Time Frame: 6 months ]
    Defined as the proportion of patients with progression free survival (PFS) i.e. absence of documented objective progression or death at 6 months after enrollment


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    Defined as the time from enrollment to the first objective documentation of disease progression or death due to any cause.

  2. Overall Survival (OS) [ Time Frame: 24 months ]
    Defined as the time from enrollment to death due to any cause.

  3. Disease Control Rate (DCR) [ Time Frame: 4 weeks ]
    Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria.

  4. Objective Response Rate (ORR) [ Time Frame: 4 weeks ]
    Defined as the proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.

  5. Pharmacokinetic profile of BBI608 and temozolomide when administered in combination with temozolomide as assessed by maximum plasma concentration and 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 ]
    Blood sampling to assess the pharmacokinetic profile (maximum plasma concentration and area under the curve) of BBI608 and temozolomide.

  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Major Eligilbility 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 (RANO) criteria
  7. ≥18 years of age.
  8. Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02315534


Locations
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United States, New York
Laura and Isaac Perlmutter Cancer Center
New York, New York, United States, 10016
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Sponsors and Collaborators
Boston Biomedical, Inc

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Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT02315534     History of Changes
Other Study ID Numbers: BBI608-251
BBI608-201GBM ( Other Identifier: Boston Biomedical, Inc. )
First Posted: December 12, 2014    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019

Keywords provided by Boston Biomedical, Inc:
GBM
Malignant Glioma

Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents