Bosutinib in Adult Patients With Recurrent Glioblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Pfizer
Information provided by (Responsible Party):
Tracy T. Batchelor, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01331291
First received: March 28, 2011
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Drug: bosutinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Phase 2 Trial of Orally Administered Bosutinib (SKI-606) in Adult Patients With Recurrent Glioblastoma (GBM)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess progression-free survival at six months in patients with recurrent GBM at first or second recurrence who are treated with continuous daily dosing of bosutinib (Arm B)


Secondary Outcome Measures:
  • Intratumoral Concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess the intratumoral concentration of bosutinib in recurrent GBM patients who are candidates for surgical re-resection (ARM A).

  • Safety Profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Overall safety profile will be characterized by type, frequency, severity (as graded by NCI CTCAE), timing and relationship of study therapy of adverse events and laboratory abnormalities. Safety and tolerability will be measured by the proportion of patients who experience Grade 3 or higher Adverse Events that are possibly, probably or definitely related to bosutinib and the number of same Adverse Events per patient. Adverse Events will be summarized by treatment for each arm by the frequency of patients experiencing treatment emergent adverse events.

  • Anti-tumor response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess anti-tumor response in patients in Arm B using MacDonald criteria.


Estimated Enrollment: 36
Study Start Date: April 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Patients who are surgical candidates
Drug: bosutinib
Taken orally
Other Name: SKI-606
Experimental: Arm B
Patients that are not surgical candidates
Drug: bosutinib
Taken orally
Other Name: SKI-606

Detailed Description:

- Arm A: Participants will receive daily doses of bosutinib orally for 7-9 days prior to surgery. On the day of the scheduled surgery (either craniotomy or surgical resection as planned by the treating doctor), participants will take the bosutinib within 6-12 hours of the surgery. During the surgery, tissue samples of the tumor will be collected to test the levels of bosutinib in the brain. A contrast-enhanced MRI or CT scan will be done within days after the surgery. Daily dosing of bosutinib will resume after a recovery period of 10 days. From then on, the study will be divided into 28-day cycles.

The following tests/procedures will be performed regularly during cycles of study treatment: medical history; physical exam; blood tests; contrast-enhanced CT or MRI scans (even numbered cycles only).

  • Arm B: Participants will receive daily doses of bosutinib. The study is divided int 28-day cycles. There are no breaks from taking bosutinib between treatment cycles. The following tests/procedures will be performed regularly during cycles of study treatment: medical history; physical exam; blood tests; contrast-enhanced CT or MRI scans (even numbered cycles only).
  • Participants may continue to receive daily bosutinib until their disease worsens, they experience unmanageable side-effects, or they decide to stop treatment.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Histologically confirmed WHO 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 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.

Exclusion Criteria:

  • Participants may not be receiving any other investigational agents
  • Previously treated with an anti-VEGF agent
  • For subjects in Arm A: if the diagnostic pathology of the biopsy specimen is not consistent with recurrent glioblastoma then the subject will be taken off study and be replaced with another subject that meets the inclusion criteria and is eligible for surgical resection
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01331291

Contacts
Contact: Tracy Batchelor, MD 617-643-1938 tbatchelor@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Tracy Batchelor, MD         
Dana=Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Andrew Norden, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Pfizer
Investigators
Principal Investigator: Tracy Batchelor, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Tracy T. Batchelor, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01331291     History of Changes
Other Study ID Numbers: 10-190
Study First Received: March 28, 2011
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
bosutinib
SKI-606

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 22, 2014