Combination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme
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|ClinicalTrials.gov Identifier: NCT01349660|
Recruitment Status : Active, not recruiting
First Posted : May 6, 2011
Results First Posted : January 31, 2018
Last Update Posted : January 31, 2018
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Drug: Bevacizumab Drug: BKM120||Phase 1 Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||88 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Study Start Date :||December 2011|
|Actual Primary Completion Date :||December 2016|
|Estimated Study Completion Date :||February 2018|
BKM 120 orally (PO) once daily (dose is 60mg or 80mg). Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks
BKM 120 orally (PO) once daily - dose is optimal dose determined in Phase I. Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks
Bevacizumab 10 mg/kg IV every 2 weeks
Other Name: Avastin
BKM120 orally (PO) once daily
Other Name: Buparlisib
- Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage [ Time Frame: Collected from day of first dose to the end of the first treatment cycle, up to 28 days ]The optimal dose of BKM120 to administer in combination with standard dose bevacizumab determined as the dose at which ≤1 of 6 patients experiences a DLT assessed using NCI CTCAE v4.03 during Cycle 1 (28 days). The optimal dose of BKM120 was determined to be 60 mg by mouth (PO), once a day for each 28 day cycle along with bevacizumab, administered 10 mg/kg intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.
- Median Progression-Free Survival (PFS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive [ Time Frame: every 8 weeks for up to 33 months ]Two groups of patients in the Phase II trial will be considered separately, 1) participants who have not received previous bevacizumab and 2) participants who have received bevacizumab as part of first-line treatment. PFS is measured from the date of first protocol treatment until date of disease progression or death occurs, or date of last adequate tumor assessment using RANO or McDonald criteria. McDonald disease progression criteria: a 25% or greater increase in sum of the diameters of lesions, new lesions, or clinical deterioration (McDonald et al, 1990). RANO disease progression criteria: a 25% or greater increase in the enhancing lesions sum compared with smallest tumor measurement, significant increase in T2/FLAIR nonenhancing lesion on stable or increasing corticosteroids, new lesions, or clinical deterioration (Wen et al 2010)
- Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive [ Time Frame: every 8 weeks, projected 24 months ]Two groups of participants in the Phase II trial will be considered separately, 1) those who have not received previous bevacizumab and 2) those who have received bevacizumab as part of first-line treatment. Overall Response (OR) = number of patients with complete or partial responses (CR or PR) per McDonald or RANO criteria. McDonald: CR as disappearance of all disease for at least four weeks, no new lesions, no steroids; PR as 50% or greater decrease in the sum of all lesions compared with baseline for at least four weeks, no new lesions, stable or reduced steroids (McDonald 1990). RANO: CR as disappearance of all disease for at least 4 weeks, no new lesions, stable or improved nonenhancing lesions, and no steroid usage; and PR as a 50% or greater decrease in the sum of all lesions compared with baseline measurement for at least four weeks, no new lesions, stable or improved nonenhancing lesions on same or lower steroid dose compared to baseline (Wen 2010).
- Median Overall Survival (OS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive [ Time Frame: every 12 weeks for up to 60 months ]Two groups of patients in the Phase II trial will be considered separately, 1) participants who have not received previous bevacizumab and 2) participants who have received bevacizumab as part of first-line treatment. Overall survival is measured as the interval from first study treatment until date of death, or date last known alive.
- Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability [ Time Frame: every 4 weeks for up to 5.2 years ]Defined as the number of participants with treatment-emergent grade 3/4/5 adverse events/serious adverse events utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.03
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01349660
|United States, Connecticut|
|Yale School of Medicine|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|Florida Cancer Specialists|
|Fort Myers, Florida, United States, 33916|
|Florida Hospital Cancer Institute|
|Orlando, Florida, United States, 32804|
|Florida Cancer Specialists|
|Saint Petersburg, Florida, United States, 33705|
|United States, Maryland|
|Center for Cancer and Blood Disorders|
|Bethesda, Maryland, United States, 20817|
|United States, Michigan|
|Grand Rapids Oncology Program|
|Grand Rapids, Michigan, United States, 49503|
|United States, Nebraska|
|Nebraska Methodist Hospital|
|Omaha, Nebraska, United States, 68114|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Kent Shih, MD||Sarah Cannon|