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Report for Clinical Trial NCT01349660

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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.

NCT01349660 Glioblastoma Multiforme
MeSH:Glioblastoma
HPO:Glioblastoma multiforme

2 Interventions

Name: Bevacizumab

Description: Bevacizumab 10 mg/kg IV every 2 weeks
Type: Drug
Group Labels: 1

BKM120/Bevacizumab

Name: BKM120

Description: BKM120 orally (PO) once daily
Type: Drug
Group Labels: 1

BKM120/Bevacizumab


Primary Outcomes

Description: 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.

Measure: Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage

Time: Collected from day of first dose to the end of the first treatment cycle, up to 28 days

Description: 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)

Measure: Median Progression-Free Survival (PFS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive

Time: every 8 weeks for up to 33 months

Secondary Outcomes

Description: 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).

Measure: Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive

Time: every 8 weeks, projected 24 months

Description: 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.

Measure: Median Overall Survival (OS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive

Time: every 12 weeks for up to 60 months

Description: 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

Measure: Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability

Time: every 4 weeks for up to 5.2 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 P13K

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



HPO Nodes


HPO: