Bosutinib in Adult Patients With Recurrent Glioblastoma

Glioblastoma Clinical Trial

Official title:

An Open Label, Phase 2 Trial of Orally Administered Bosutinib (SKI-606) in Adult Patients With Recurrent Glioblastoma (GBM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01331291
• Other study ID #: 10-190
• Status: Completed
• Phase: Phase 2
• First received: March 28, 2011
• Last updated: April 30, 2015
• Start date: April 2011
• Est. completion date: December 2014

Study information

• Verified date: April 2015
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• bosutinib
Taken orally

Locations

Country	Name	City	State
United States	Dana=Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Brigham and Women's Hospital, Dana-Farber Cancer Institute, Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival	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)	2 years	No
Secondary	Intratumoral Concentration	Assess the intratumoral concentration of bosutinib in recurrent GBM patients who are candidates for surgical re-resection (ARM A).	2 years	No
Secondary	Safety Profile	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.	2 years	Yes
Secondary	Anti-tumor response	Assess anti-tumor response in patients in Arm B using MacDonald criteria.	2 years	No