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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Glioblastoma

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Trial Information

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


- 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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Progression-Free Survival

Outcome Description:

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)

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Tracy Batchelor, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital

Authority:

United States: Food and Drug Administration

Study ID:

10-190

NCT ID:

NCT01331291

Start Date:

April 2011

Completion Date:

October 2012

Related Keywords:

  • Glioblastoma
  • bosutinib
  • SKI-606
  • Glioblastoma

Name

Location

Massachusetts General HospitalBoston, Massachusetts  02114-2617
Dana=Farber Cancer InstituteBoston, Massachusetts  02115