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

Study Purpose

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.

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:

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.

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.

NCT01349660
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 1/Phase 2
Lead Sponsor

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

SCRI Development Innovations, LLC
Principal Investigator

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

Kent Shih, MD
Principal Investigator Affiliation Sarah Cannon
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 Multiforme
Additional Details

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).

Arms & Interventions

Arms

Experimental: BKM120/Bevacizumab

Phase I: BKM 120 orally (PO) once daily (dose is 60mg or 80mg). Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks Phase II: BKM 120 orally (PO) once daily - dose is optimal dose determined in Phase I. Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks

Interventions

Drug: - Bevacizumab

Bevacizumab 10 mg/kg IV every 2 weeks

Drug: - BKM120

BKM120 orally (PO) once daily

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.

Yale School of Medicine, New Haven, Connecticut

Status

Address

Yale School of Medicine

New Haven, Connecticut, 06520

Florida Cancer Specialists, Fort Myers, Florida

Status

Address

Florida Cancer Specialists

Fort Myers, Florida, 33916

Florida Hospital Cancer Institute, Orlando, Florida

Status

Address

Florida Hospital Cancer Institute

Orlando, Florida, 32804

Florida Cancer Specialists, Saint Petersburg, Florida

Status

Address

Florida Cancer Specialists

Saint Petersburg, Florida, 33705

Center for Cancer and Blood Disorders, Bethesda, Maryland

Status

Address

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817

Grand Rapids Oncology Program, Grand Rapids, Michigan

Status

Address

Grand Rapids Oncology Program

Grand Rapids, Michigan, 49503

Nebraska Methodist Hospital, Omaha, Nebraska

Status

Address

Nebraska Methodist Hospital

Omaha, Nebraska, 68114

Tennessee Oncology, Nashville, Tennessee

Status

Address

Tennessee Oncology

Nashville, Tennessee, 37203