BKM120 as Second-line Therapy for Advanced Endometrial Cancer

Study Overview
=================
Brief Summary
-----------------
This is a prospective multi-center, open-label, single arm, Phase II study to investigate the safety and efficacy of BKM120 in patients with advanced endometrial carcinoma whose disease progressed on or after a first-line antineoplastic treatment. Patients will receive BKM120 orally at a dose of 100 mg/day. Availability of tumor specimen (either archival tissue or a fixed fresh biopsy) is mandatory for assessment of the PI3K (Phosphatidylinositol 3 Kinase (PI3K) pathway activation status.

Official Title
-----------------
A Phase II, Single-arm Study of Orally Administered BKM120 as Second-line Therapy in Patients With Advanced Endometrial Carcinoma

Conditions
-----------------
Advanced Endometrial Cancer

Intervention / Treatment
-----------------
* Drug: BKM120


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2 histologically confirmed diagnosis of advanced endometrial carcinoma with available tissue specimen for identification of PI3K pathway activation (archival tissue or a fixed fresh biopsy) one prior line of antineoplastic treatment with a cytotoxic agent objective progression of disease after prior treatment and at least one measurable lesion as per RECIST criteria adequate bone marrow and organ function Exclusion Criteria: previous treatment with PI3K and/or mTOR inhibitors symptomatic CNS metastases concurrent malignancy or malignancy within 3 years of study enrollment Active mood disorder as judged by investigator or medically documented history of mood disorder (e.g. major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, etc.), ≥ CTCAE grade 3 anxiety pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment in the study poorly controlled diabetes mellitus (HbA1c > 8 %) history of cardiac dysfunction or active cardiac disease as specified in the protocol impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Patients<br> | Drug: BKM120<br> <br> * Other names: Buparlisib;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) According to PI3K Activation Pathway Status | PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 24 months | 
| Overall Survival (OS) According to PI3K Activation Pathway Status | Overall survival (OS) was defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced endometrial cancer, PI3K pathway, second-line treatment