AzTrials
AzTrials

GlioblastomaPhase 2NCT01331291

Bosutinib in Adult Patients With Recurrent Glioblastoma

A Phase 2 study testing bosutinib in people with Glioblastoma, run by Massachusetts General Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
bosutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
2 sitesUnited States
Study dates
Apr 2011to Dec 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 14Show fewer
  • 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.

Who cannot join

  • 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
Show all 13Show fewer
  • 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 locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana=Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

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

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.

Read the 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.
Conditions
Glioblastoma
Being tested
bosutinib
Keywords
bosutinib, SKI-606
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bosutinibDrug

    Also called SKI-606

    Taken orally

Study groups in NCT01331291
Study groupRoleWhat they receive
Arm AExperimentalPatients 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.
Receives: Drug: bosutinib
Arm BExperimentalPatients 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.
Receives: Drug: bosutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Secondary outcomes (3)

  1. Intratumoral Concentration

    Assess the intratumoral concentration of bosutinib in recurrent glioblastoma patients who are candidates for surgical re-resection (ARM A).

    Measured: 2 years

  2. 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.

    Measured: 2 years

  3. Anti-tumor Response

    Assess anti-tumor response in patients in Arm B using MacDonald criteria. There are four possible responses: complete response, partial response, stable disease, or progressive disease. Criteria are based on measurements of tumor dimension as visualized with a contrast-enhanced MRI.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2011 (estimated)
  2. Study startApr 2011
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01331291
Sponsor's protocol ID
10-190
Status last verified
Jun 2016
First submitted
28 Mar 2011
Last updated
25 Jul 2016
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 25411098

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bosutinib in people with Glioblastoma, run by Massachusetts General Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01331291, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in