Glioblastoma Multiforme
Conditions
Keywords
Glioblastoma multiforme, GBM, Bevacizumab, PI3K Pathway, BKM120
Brief summary
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.
Detailed description
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).
Interventions
DRUGBevacizumab
Bevacizumab 10 mg/kg IV every 2 weeks
DRUGBKM120
BKM120 orally (PO) once daily
Sponsors
Novartis
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage | 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 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 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 | 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 | 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 |
Countries
United States
Participant flow
Recruitment details
Between Oct 2011 and May 2012, 12 participants with refractory solid tumors were enrolled into the Phase I dose escalation trial from 3 U.S. investigational sites. Once a maximum tolerated dose was assigned, from Jul 2012 to Jun 2016, 76 patients with glioblastoma multiforme were enrolled in the Phase II trial from 7 U.S investigational sites
Participants by arm
| Arm | Count |
|---|---|
| Phase I - Dose Level 1 (60 mg BKM, 10mg/kg Bevacizumab) BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle
Phase I patients include those diagnosed with advanced, metastatic solid tumors. | 6 |
| Phase I - Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) BKM120: 80mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.
Phase I patients include those diagnosed with advanced, metastatic solid tumors. | 6 |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.
Phase II patients include those with progressive glioblastoma multiforme | 76 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 12 |
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Declining Performance Status | 0 | 0 | 1 |
| Overall Study | Disease Progression | 2 | 4 | 50 |
| Overall Study | Non-Permitted Interventions | 0 | 0 | 2 |
| Overall Study | Still Receiving Study Treatment | 0 | 0 | 1 |
| Overall Study | Study Compliance | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 9 |
Baseline characteristics
| Characteristic | Total | Phase I - Dose Level 1 (60 mg BKM, 10mg/kg Bevacizumab) | Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Phase I - Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) |
|---|---|---|---|---|
| Age, Continuous | 57 years | 61 years | 57 years | 64 years |
| Primary Tumor Type Colorectal | 5 Participants | 2 Participants | 0 Participants | 3 Participants |
| Primary Tumor Type Glioblastoma Multiforme | 81 Participants | 2 Participants | 76 Participants | 3 Participants |
| Primary Tumor Type Lung | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Prior Treatment with Bevacizumab Bevacizumab Naive | 57 Participants | — | 57 Participants | — |
| Prior Treatment with Bevacizumab Prior Bevacizumab Treatment | 19 Participants | — | 19 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 82 Participants | 6 Participants | 70 Participants | 6 Participants |
| Region of Enrollment United States | 88 participants | 6 participants | 76 participants | 6 participants |
| Sex: Female, Male Female | 40 Participants | 2 Participants | 36 Participants | 2 Participants |
| Sex: Female, Male Male | 48 Participants | 4 Participants | 40 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 75 / 76 |
| serious Total, serious adverse events | 3 / 6 | 2 / 6 | 27 / 76 |
Outcome results
Primary
Median Progression-Free Survival (PFS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive
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)
Time frame: every 8 weeks for up to 33 months
Population: All Phase II patients receiving at least one dose of study treatment that have had at least one post-baseline disease assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Median Progression-Free Survival (PFS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 2.8 months |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Median Progression-Free Survival (PFS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 5.3 months |
Primary
Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage
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.
Time frame: Collected from day of first dose to the end of the first treatment cycle, up to 28 days
Population: Includes all Phase I patients receiving assigned study dosing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage | 3 Participants |
Secondary
Median Overall Survival (OS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive
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.
Time frame: every 12 weeks for up to 60 months
Population: Participants that have received at least one dose of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Median Overall Survival (OS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 6.6 months |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Median Overall Survival (OS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 10.8 months |
Secondary
Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability
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
Time frame: every 4 weeks for up to 5.2 years
Population: Includes all participants that received at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Fatigue | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Confusion | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyperglycemia | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Diarrhea | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Alanine aminotransferase increased | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypertension | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Seizure | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Asthenia | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Aspartate Aminotransferase Increased | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypertriglyceridemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Abdominal pain | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Altered Mental Status | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Gait Disturbance | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Ataxia | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Muscle Weakness | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Pneumonia | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Sepsis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Respiratory Failure | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Thrombocytopenia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypercholesterolemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Mucositis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Anorexia | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Memory Impairment | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Pruritis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Vomiting | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Mood Alteration | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Weight Loss | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dehydration | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dyspnea | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hemorrhage | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Somnolence | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Taste Alteration | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Agitation | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Fall | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypermagnesemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Ejection Fraction Decreased | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Elevated Liver Enzymes | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypoalbuminemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypophosphatemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Psychosis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Suicidal Ideation | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Thromboembolic Event | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Akathisia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Cellulitis | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Chronic Obstructive Pulmonary Disease | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Delirium | 1 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Diabetic Ketoacidosis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Enteritis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Female Genital Tract Fistula | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Gastrointestinal Infection | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyperlipidemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Intracranial Hemorrhage | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Left Ventricular Systolic Dysfunction | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Necrotizing Fasciitis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Palsy | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Paralysis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Personality Change | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Syncope | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Transaminitis | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Urine Output Decreased | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Vaginal Fistula | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Headache | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypokalemia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyponatremia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Nausea | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Proteinuria | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Rash | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Urinary Tract Infection | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Lipase Increased | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Neutropenia | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dysarthria | 0 Participants |
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Volume Depletion | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Paralysis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Mood Alteration | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Weight Loss | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Neutropenia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Personality Change | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dehydration | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dyspnea | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hemorrhage | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Syncope | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Somnolence | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Taste Alteration | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Rash | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Agitation | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Transaminitis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Fall | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypermagnesemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Ejection Fraction Decreased | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Urine Output Decreased | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Elevated Liver Enzymes | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypoalbuminemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dysarthria | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypophosphatemia | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Vaginal Fistula | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Psychosis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Volume Depletion | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Suicidal Ideation | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Thromboembolic Event | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Urinary Tract Infection | 2 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Akathisia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Headache | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Cellulitis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Chronic Obstructive Pulmonary Disease | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Delirium | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypokalemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Diabetic Ketoacidosis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Enteritis | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Fatigue | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Confusion | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Diarrhea | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyperglycemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Female Genital Tract Fistula | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Alanine aminotransferase increased | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyponatremia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Gastrointestinal Infection | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Seizure | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Asthenia | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Aspartate Aminotransferase Increased | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyperlipidemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypertriglyceridemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Abdominal pain | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Altered Mental Status | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Intracranial Hemorrhage | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Gait Disturbance | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Ataxia | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Lipase Increased | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Nausea | 2 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Muscle Weakness | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Left Ventricular Systolic Dysfunction | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Pneumonia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Sepsis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Respiratory Failure | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Necrotizing Fasciitis | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Thrombocytopenia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypercholesterolemia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypertension | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Mucositis | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Palsy | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Anorexia | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Memory Impairment | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Proteinuria | 0 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Pruritis | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Vomiting | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Gait Disturbance | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Vomiting | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Paralysis | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Intracranial Hemorrhage | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Mood Alteration | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Proteinuria | 3 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Fatigue | 8 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Weight Loss | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Enteritis | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Neutropenia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Mucositis | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Confusion | 8 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dehydration | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Personality Change | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Ataxia | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dyspnea | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Vaginal Fistula | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Pruritis | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hemorrhage | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyperglycemia | 5 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Lipase Increased | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Somnolence | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Syncope | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Female Genital Tract Fistula | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Taste Alteration | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Thrombocytopenia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Alanine aminotransferase increased | 5 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Agitation | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Dysarthria | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Necrotizing Fasciitis | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypertension | 6 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Fall | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Transaminitis | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Muscle Weakness | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypermagnesemia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Rash | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Memory Impairment | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Ejection Fraction Decreased | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Seizure | 6 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Gastrointestinal Infection | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Elevated Liver Enzymes | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Urine Output Decreased | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypercholesterolemia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypoalbuminemia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Asthenia | 4 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyponatremia | 3 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypophosphatemia | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Pneumonia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Aspartate Aminotransferase Increased | 5 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Psychosis | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Left Ventricular Systolic Dysfunction | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Anorexia | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Suicidal Ideation | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Volume Depletion | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypertriglyceridemia | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Thromboembolic Event | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hyperlipidemia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Sepsis | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Akathisia | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Abdominal pain | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Diarrhea | 5 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Cellulitis | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Headache | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Nausea | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Chronic Obstructive Pulmonary Disease | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Urinary Tract Infection | 2 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Altered Mental Status | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Delirium | 0 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Palsy | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Respiratory Failure | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Diabetic Ketoacidosis | 1 Participants |
| Phase II - (60 mg BKM120, 10mg/kg Bevacizumab) | Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability | Hypokalemia | 4 Participants |
Secondary
Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive
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).
Time frame: every 8 weeks, projected 24 months
Population: Includes participants in Phase II that receive at least one study treatment and have at least one post-baseline disease assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab) | Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 1 Participants |
| Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab) | Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive | 18 Participants |