Bosutinib in Adult Patients With Recurrent Glioblastoma

NCT01331291 | Completed Phase 2 Results DMC

• 1 other identifier: 10-190
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

For many brain tumors, one reason that chemotherapy drugs might not be effective is that the drug may not be able to get into the brain tumor and kill the cancer cells. The brain is protected by a layer called the blood brain barrier. This barrier prevents substances from entering. The purpose of this research study is to determine if bosutinib can get past the blood brain barrier and into the brain tumor, and to see how well bosutinib works in killing cancer cells.

Conditions

Glioblastoma

Keywords

bosutinib; SKI-606

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Assess progression-free survival at six months in patients with recurrent glioblastoma at first or second recurrence who are treated with continuous daily dosing of bosutinib (Arm B). Progression-free survival is measured from initiation of study treatment to date of progression.

  2 years

Secondary Outcomes (3)

• Intratumoral Concentration

  2 years

• Safety Profile

  2 years

• Anti-tumor Response

  2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Patients who are surgical candidates. Participants are given oral bosutinib, 400mg daily, for 7-9 days prior to resection. After at least 10 days elapsed post-operatively, bosutinib dosing was resumed.

Drug: bosutinib

Arm B

EXPERIMENTAL

Patients that are not surgical candidates. Participants are given oral bosutinib, 400 mg daily in 28 day cycles until disease progression, intolerability or withdrawal of consent.

Drug: bosutinib

Interventions

bosutinib DRUG

Taken orally

Also known as: SKI-606

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• years of age or older
• Histologically confirmed WHO (World Health Organization) grade IV astrocytoma (glioblastoma). Patients with recurrent disease whose original pathology confirmed glioblastoma will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation to GBM.
• The first-line regimen must have included, at a minimum, temozolomide and radiation.
• First or second episode of progressive disease.
• No more than two prior treatment regimens for progressive disease. Concurrent temozolomide and radiation followed by monthly cycles of temozolomide is counted as one regimen.
• For all study arms, patients must have at least 15 unstained slides or 1 tissue block available from a prior biopsy or surgery.
• All patients must have progressive disease on contrast-enhanced brain CT or MRI as defined by MacDonald Criteria, or have documented recurrent glioblastoma on diagnostic biopsy. Arm A patients may continue treatment in the post-operative period even if there is no residual contrast-enhancing tumor after surgery.
• For Arm A, patients must be candidates for surgical partial or gross-total resection.
• Interval of at least 2 weeks between prior surgical resection and adequate wound healing.
• Interval of at least 12 weeks from prior radiotherapy unless there is either a) histopathologic confirmation of recurrent tumor; b) new enhancement on MRI outside of the XRT (external beam radiation therapy) treatment field.
• Patients must have sufficient time for recovery from prior therapy
• Karnofsky Performance Status of 60% or greater
• Laboratory levels as outlined in the protocol
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months thereafter.

You may not qualify if:

• Participants may not be receiving any other investigational agents
• Previously treated with an anti-VEGF (anti-vascular endothelial growth factor) agent
• Any surgery within 2 weeks of baseline disease assessments, or not fully recovered from any side effects of previous procedures
• Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medications in tablet form.
• Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
• Concomitant use of CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration
• Concomitant use of CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs during treatment phase of the study and within 2 weeks prior to starting treatment.
• Uncontrolled or significant cardiovascular disease
• Prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery
• Pregnant or breast feeding women
• HIV-positive individuals on combination antiretroviral therapy
• Other severe acute or chronic medical condition or laboratory abnormality

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Pfizer: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana=Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Taylor JW, Dietrich J, Gerstner ER, Norden AD, Rinne ML, Cahill DP, Stemmer-Rachamimov A, Wen PY, Betensky RA, Giorgio DH, Snodgrass K, Randall AE, Batchelor TT, Chi AS. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. J Neurooncol. 2015 Feb;121(3):557-63. doi: 10.1007/s11060-014-1667-z. Epub 2014 Nov 20.

  PMID: 25411098 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

bosutinib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This study met pre-specified criteria for early closure, as all 9 patients enrolled on Arm B demonstrated disease progression within 6 months.

Results Point of Contact

• Title: Tracy T. Batchelor, MD
• Organization: Massachusetts General Hospital

tbatchelor@mgh.harvard.edu

617-643-1938

Study Officials

• Tracy Batchelor, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2011
• First Posted: April 8, 2011
• Study Start: April 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 25, 2016
• Results First Posted: June 20, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)