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 |
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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 (Post-text Supplement 1, Novartis guidelines based on RECIST Version 1.1) in patients with advanced endometrial carcinoma who exhibit PI3K pathway activation. |
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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 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
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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 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: 5. Patient has at least one measurable lesion as per RECIST criteria (Post-text Supplement 1) 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 |
1. 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 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) 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 11. Patient has a history of cardiac dysfunction 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 12-3 in Appendix 3 for a list of prohibited drugs) 13. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) 14. Patient receiving chronic treatment with steroids or another immunosuppressive agent. 15. Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment contraindicate her participation in the clinical study (e.g., chronic pancreatitis, active chronic hepatitis etc.) 16. Patient has a history of non-compliance to medical regimen 17. Patient is currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Table 12-1 in Appendix 1 for a list of prohibited CYP 3A4 inhibitors and inducers. 18. Patient has a known history of HIV (testing not mandatory) infection 19. Patient is a pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum hCG laboratory test (> 5 mIU/mL) 20. Patient is a woman of child-bearing potential, |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR per RECIST* in patients with PI3K pathway activation 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
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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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 |
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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 |