E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced endometrial carcinoma whose disease progressed on or after a first-line antineoplastic treatment. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007064 |
E.1.2 | Term | Cancer of endometrium metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 (Appendix 5, Novartis guidelines based on RECIST Version 1.1) in patients with advanced endometrial carcinoma who exhibit PI3K pathway activation defined as the presence of a PIK3CA and/or PTEN mutation and/or PTEN negative by IHC (less than 10% staining). • To demonstrate the efficacy of BKM120 as measured by Objective Response Rate (ORR) per RECIST (Appendix 5) in all patients enrolled in the study. |
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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 a non-activated 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has provided a signed Informed Consent Form (ICF) obtained prior to any screening procedure 2. Patient is a female ≥ 18 years at the day of consenting to the study 3. Patient has a histologically confirmed diagnosis of advanced endometrial carcinoma with available tissue specimen, either archival tissue (one block or a minimum of 20 unstained slides) or a fixed fresh biopsy, for identification of PI3K pathway activation • all of the following histological types are eligible: endometrioid, papillary serous, clear cell, papillary endometrioid, mucinous, and adenosquamous • confirmation that the specimen has been collected by the courier service and will be sent to the central lab (e.g., tracking number of courier service) must be communicated to the sponsor prior to enrolling the patient into the treatment phase of the trial 4. Patient has experienced objective progression of disease after first-line antineoplastic treatment for advanced endometrial carcinoma as defined by the investigator. One prior line of antineoplastic treatment is defined as: • First-line treatment for advanced disease including at least one cytotoxic agent. Note: any adverse events related to prior therapy must have returned to grade ≤ 1 (except alopecia) before screening procedures are initiated • Any adjuvant treatment is generally not considered a prior line of treatment unless the recurrence occurred while on adjuvant chemotherapy or ≤ 6 months since the last administration of adjuvant chemotherapy (with the exception of endocrine treatments), • Any prior hormonal treatment is not considered a line of treatment in any setting 5. Patient has at least one measurable lesion as per RECIST criteria (Appendix 5) 6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 7. Patient has adequate bone marrow and organ function as defined by the following laboratory values: • Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L • Platelets ≥ 100 x 109/L • Hemoglobin ≥ 9.0 g/dL • INR ≤ 2 - Potassium, calcium, magnesium within normal limits for the institution • Serum Creatinine ≤ 1.5 x ULN • Serum Bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN) • AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present • Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L |
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E.4 | Principal exclusion criteria |
Patient has received previous treatment with PI3K and/or mTOR inhibitors 2. Patient has received more than one line of antineoplastic treatment for advanced disease (for definition of prior lines of therapy please refer to inclusion criterion 4) 3. Patient has symptomatic CNS metastases • Patients with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to enrollment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases. 4. Patient has a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer) 5. Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of ‘1, 2, or 3’ to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9) • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) • ≥ CTCAE grade 3 anxiety 6. Patient is concurrently using other approved or investigational antineoplastic agent (hormonal agents included) 7. Patient has received pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment in this study or has not recovered from side effects of such therapy at the time of initiation of screening procedures. 8. Patient has had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery 9. Patient has poorly controlled diabetes mellitus (HbA1c > 8 %) 10. Patient has active cardiac disease including any of the following: • Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated 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 arrythmias requiring a pacemaker or not controlled with medication • Conduction abnormality requiring a pacemaker • Valvular disease with documented compromise in cardiac function • Symptomatic pericarditis 11. Patient has a history of cardiac dysfunction including any of the following; • Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function • History of documented congestive heart failure (New York Heart Association functional classification III-IV) • Documented cardiomyopathy 12. Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug (see Section 5.1.5.3 and Table 13-3 in Appendix 3 for a list of prohibited drugs). See section 4.2 of the protocol for the remaining criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- ORR per RECIST in patients with PI3K pathway activation. PI3K pathway activation is defined as PIK3CA mutation and/or PTEN gene mutation and/or PTEN negative by IHC (less than 10% staining) - ORR per RECIST |
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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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
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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
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L’analisi finale sara` eseguita in almeno 140 pazienti valutabili. Il trattamento con BKM120 continuera` fino a quando le pazienti ne avranno beneficio secondo l`opinione del medico. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |