Advanced Endometrial Cancer
Conditions
Keywords
Advanced endometrial cancer, PI3K pathway, second-line treatment
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.
Interventions
DRUGBKM120
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | 24 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) According to PI3K Activation Pathway Status | 24 months | 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. |
| Overall Survival (OS) According to PI3K Activation Pathway Status | 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 | 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 |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Italy, Japan, Poland, Russia, Singapore, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 24 |
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive Disease | 41 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 9.04 |
| Sex/Gender, Customized Female | 70 participants |
| Sex/Gender, Customized Male | 0 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 67 / 70 |
| serious Total, serious adverse events | 33 / 70 |
Outcome results
Primary
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
Time frame: 24 months
Population: Full analysis set includes all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Complete Response (CR) | 1 number of participants |
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Progressive disease (PD) | 20 number of participants |
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Stable Disease (SD) | 19 number of participants |
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Patients with Measurable disease at baseline | 49 number of participants |
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Overall Response Rate (CR + PR) | 1 number of participants |
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Unknown (UNK) | 9 number of participants |
| Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Partial Response (PR) | 0 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Stable Disease (SD) | 7 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Patients with Measurable disease at baseline | 21 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Complete Response (CR) | 0 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Partial Response (PR) | 1 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Progressive disease (PD) | 9 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Unknown (UNK) | 4 number of participants |
| Non-Activated Pl3K | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Overall Response Rate (CR + PR) | 1 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Progressive disease (PD) | 29 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Complete Response (CR) | 1 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Overall Response Rate (CR + PR) | 2 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Unknown (UNK) | 13 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Stable Disease (SD) | 26 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Partial Response (PR) | 1 number of participants |
| All Patients | Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status | Patients with Measurable disease at baseline | 70 number of participants |
Secondary
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
Time frame: 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
Population: Full analysis set includes all patients who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Activated Pl3K | Overall Survival (OS) According to PI3K Activation Pathway Status | 8.9 months |
| Non-Activated Pl3K | Overall Survival (OS) According to PI3K Activation Pathway Status | 14.2 months |
| All Patients | Overall Survival (OS) According to PI3K Activation Pathway Status | 9.9 months |
Secondary
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.
Time frame: 24 months
Population: Full analysis set includes all patients who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Activated Pl3K | Progression Free Survival (PFS) According to PI3K Activation Pathway Status | 1.9 months |
| Non-Activated Pl3K | Progression Free Survival (PFS) According to PI3K Activation Pathway Status | 1.9 months |
| All Patients | Progression Free Survival (PFS) According to PI3K Activation Pathway Status | 1.9 months |