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Bosutinib in Adult Patients With Recurrent Glioblastoma

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 18 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.

Exclusion Criteria:

  • - Participants may not be receiving any other investigational agents.
  • - Previously treated with an anti-VEGF (anti-vascular endothelial growth factor) 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01331291
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Massachusetts General Hospital
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Tracy Batchelor, MD
Principal Investigator Affiliation Massachusetts General Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma
Additional Details

  • - 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.

Arms & Interventions

Arms

Experimental: Arm A

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.

Experimental: Arm B

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.

Interventions

Drug: - bosutinib

Taken orally

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Massachusetts General Hospital, Boston, Massachusetts

Status

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Dana=Farber Cancer Institute, Boston, Massachusetts

Status

Address

Dana=Farber Cancer Institute

Boston, Massachusetts, 02115