BKM120 for Patients With PI3K-activated Tumors

Study Overview
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Brief Summary
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The purpose of this signal seeking study was is to determine whether treatment with BKM120 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

Official Title
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Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 1 - BKM120 for Patients With PI3K-activated Tumors

Conditions
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PI3K Pathway Activated Tumors

Intervention / Treatment
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* Drug: BKM120


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient had a confirmed diagnosis of a solid tumor or hematological malignancy with the exception of endometrial cancer, glioblastoma, nonsmall cell lung cancer, prostate cancer or breast cancer. Patient's tumor was evaluated and pre-identified to have activation of the PI3K pathway, at a CLIA certified laboratory Patient must have received at least one prior treatment for recurrent metastatic and /or locally advanced disease and for whom no standard therapy options was anticipated to result in a durable remission. Patient must have had progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Exclusion Criteria: Patient had received previous treatment with BKM120 Patient had symptomatic CNS metastases Patient had mood disorder as outlined in Section 5 Patient had received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BKM120<br>BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28- day cycle | Drug: BKM120<br>* BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Clinical Benefit Response Rate | Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at >=16 weeks. For hematologic tumors other appropriate hematological response criteria was applied. Response criteria: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm., PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters | Overall Response (OR) of Partial Response (PR) or greater is based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria apply | baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months | 
| Progression-Free Survival - Number of Participants With an Event | Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause | Every 8 Weeks until death, assessed up to 24 months | 
| Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in Months | Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause | baseline up to 24 months | 
| Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause. | baseline up to 24 months | 
| Overall Survival - Number of Participants With an Event | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact | Every 8 Weeks until death, assessed up to 24 months | 
| Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact | baseline up to 24 months | 
| Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact | baseline up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PI3K pathway activation, Solid tumor, malignancy, hematologic malignancy, P13K activated tumors, BKM120, signature, AML, acute myelogenous leukemia, cervical, ovarian, hepatobiliary, buparlisib