A Phase II, single-arm study of orally administered BKM120 as second-line therapy in patients with advanced endometrial carcinoma
- Conditions
- Patients who have experienced progression of disease after first-line antineoplasic treatment of advanced endometrial carcinoma
- Registration Number
- EUCTR2010-022015-19-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 140
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: •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<br>•To determine Time to Response (TTR)<br>•To determine Duration of Response <br>•To determine Progression Free Survival (PFS)<br>•To assess Overall Survival (OS)<br>•To evaluate the safety of BKM120<br>;Primary end point(s): ORR per RECIST* in patients with PI3K pathway activation<br>ORR per RECIST
- Secondary Outcome Measures
Name Time Method