E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients who have experienced progression of disease after first-line antineoplasic treatment of advanced endometrial carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Endometrial Cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of BKM120 as measured by Objective
Response Rate (ORR) per RECIST in patients with advanced endometrial
carcinoma who exhibit PI3K pathway activation.
To demonstrate the efficacy of BKM120 as measured by ORR per RECIST
in all patients enrolled in the study
|
|
E.2.2 | Secondary objectives of the trial |
• To determine the efficacy of BKM120 as measured by Objective
Response Rate (ORR) per RECIST in patients with advanced endometrial
carcinoma who exhibit non-activated/ unknown PI3K pathway
• To determine Time to Response (TTR)
• To determine Duration of Response
• To determine Progression Free Survival (PFS)
• To assess Overall Survival (OS)
• To evaluate the safety of BKM120
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
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)
3. one prior line of antineoplastic treatment with a cytotoxic agent
4. objective progression of disease after prior treatment and at least one
measurable lesion as per RECIST criteria
5. adequate bone marrow and organ function |
|
E.4 | Principal exclusion criteria |
1. previous treatment with PI3K and/or mTOR inhibitors
2. symptomatic CNS metastases
3. concurrent malignancy or malignancy within 3 years of study
enrollment
4. 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
5. pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment
in the study
6.poorly controlled diabetes mellitus (HbA1c > 8 %)
7. history of cardiac dysfunction or active cardiac disease as specified in
the protocol
8. impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of BKM120
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
ORR per RECIST in patients with PI3K pathway activation
ORR per RECIST |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
based on Full Analysis Set (FAS) and based on investigator RECIST
evaluations
|
|
E.5.2 | Secondary end point(s) |
ORR per RECIST in patient with non-activated PI3K pathway
TTR per RECIST
Duration of Response per RECIST
PFSA per RECIST
OS
Frequency and severity of Adverse Events
Number of lab values worsening from baseline based on CTCAE grade
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
based on Primary Analysis Set |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Canada |
France |
Germany |
Italy |
Poland |
Russian Federation |
Spain |
Turkey |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The final analysis will occur once at least 140 evaluable patients. Any patients receiving study treatment at that time will continue to receive BKM120 for as long as they continue to receive benefit in the opinion of the investigator |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 5 |