Combination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme



Status:Active, not recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:2/2/2018
Start Date:December 2011
End Date:February 2018

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Phase I/II Study of the Combination of BKM120 and Bevacizumab in Patients With Refractory Solid Tumors (Phase I) and Relapsed/Refractory Glioblastoma Multiforme (Phase II)

In this phase I/II study,investigators are evaluating the feasibility and efficacy of the
combination of BKM120, an oral inhibitor of PI3 kinase, and bevacizumab in the treatment of
patients with relapsed/refractory GBM. In the Phase I part of the trial, the optimal BKM120
dose to be administered with a standard dose of bevacizumab will be determined in patients
with refractory solid tumors. Although it is unlikely that the concurrent administration of
bevacizumab will alter the pharmacokinetics of BKM120, limited pharmacokinetic sampling will
be performed on all patients treated during the Phase II portion of the study. Assuming this
combination is feasible, the Phase II portion of the study will proceed, using the doses
determined in the Phase I portion. In the phase II portion, eligible patients will be limited
to those with recurrent/progressive GBM following 1st line combined modality therapy.

This is an open-label, non-randomized Phase I study of patients with advanced refractory
solid tumors followed by a Phase II study for the second-line treatment of patients with
relapsed/refractory glioblastoma multiforme.

In the phase I part of the study the optimal dose of BKM120 when combined with bevacizumab
was determined. In the Phase II part of this study, patients with relapsed/refractory GBM
following first line therapy are being treated with the BKM120/bevacizumab combination.
Limited BKM120 pharmacokinetic evaluation will be performed on all patients treated during
this part of the study. Patients will be reevaluated for response to treatment after 2 cycles
(8 weeks). Patients with objective response or stable disease will continue treatment, with
subsequent reevaluations every 8 weeks, until disease progression or unacceptable toxicity
occurs.

Two populations of patients with relapsed/refractory GBM will be treated in the Phase II
trial: 1) patients with no previous exposure to bevacizumab (N= 55) and 2) patients who
received bevacizumab as part of first-line combined modality treatment (N= 20).

Inclusion Criteria:

Phase I ONLY:

- Advanced, metastatic solid tumor that has progressed after standard therapy, or is a
tumor type resistant to therapy, and for which bevacizumab is clinically appropriate.

- Patient may have measurable disease or non-measureable disease as defined by RECIST
v1.1 criteria

Phase II ONLY:

- Progressive GBM after treatment with surgical resection (if possible) and 1st line
radiation/chemotherapy.

- No previous treatment with a PI3K inhibitor. Previous treatment with bevacizumab as a
component of first-line therapy is allowed.

- At least one measurable or evaluable lesion definable by MRI scan. Disease must be
measurable by RANO criteria.

- Archival tumor tissue available for correlative testing.

ALL PATIENTS:

- Patient must be ≥ 4 weeks from administration of last dose of cancer therapy
(including radiation therapy, biologic therapy, hormonal therapy, or chemotherapy).
Patients who receive a small molecule targeted therapy as part of their first line
treatment regimen must be ≥ 4 weeks or ≥ 5 half lives from administration of last
dose, whichever is shorter. The patient must have recovered from or come to a new
chronic or stable baseline from all treatment-related toxicities.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

- Life expectancy of ≥ 3 months.

- Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

- Patients with diarrhea ≥ grade 2.

- Patients with uncontrolled type I or type II diabetes mellitus, defined as a fasting
plasma glucose ≥120 mg/dL.

- Patients who have received prior treatment with a P13K inhibitor.

- Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose
of 1 mg allowed for port line patency permitted).

- Patient has active cardiac disease including any of the following:

- Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated
acquisition (MUGA) scan or echocardiogram (ECHO)

- QTc > 480 msec on screening ECG (using the QTcF formula)

- Angina pectoris that requires the use of anti-anginal medication

- Ventricular arrhythmias except for benign premature ventricular contractions

- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication

- Conduction abnormality requiring a pacemaker

- Valvular disease with documented compromise in cardiac function

- Symptomatic pericarditis

- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug.

- Patients with clinical history of hemoptysis or hematemesis (defined as having bright
red blood of ½ teaspoon or more per episode) ≤1 month prior to study enrollment.

- Patients with any history of a bleeding diathesis or coagulopathy (in the absence of
therapeutic anticoagulation)

- Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial.

- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy.

- Patients who have been treated with any hematopoietic colony-stimulating factors (e.g.
G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin
therapy, if initiated at least 2 weeks prior to enrollment may be continued.

- Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt
or significant traumatic injury ≤ 28 days prior to entry.
We found this trial at
8
sites
8303 Dodge Street
Omaha, Nebraska 68114
(402) 354–4000
Nebraska Methodist Hospital Methodist Hospital is a general medical and surgical hospital in Omaha, NE....
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3840 Broadway
Fort Myers, Florida 33901
(239) 275-6400
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Fort Myers, FL
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6410 Rockledge Dr #660
Bethesda, Maryland 20817
(301) 571-0019
Center for Cancer & Blood Disorders Widely recognized for its compassionate, expert care, the Center...
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Grand Rapids, Michigan 49503
Principal Investigator: Gilbert Padula, MD
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250 25th Ave N, Ste 100
Nashville, Tennessee 37023
615-320-5090
Tennessee Oncology, PLLC Since 1976 Tennessee Oncology has been providing quality cancer care. In 2013,...
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New Haven, Connecticut 06520
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Orlando, Florida 32804
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Saint Petersburg, Florida 33705
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Saint Petersburg, FL
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