triple negative metastatic breast cancer MedDRA version: 14.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BKM 120 - capsules 10 mg
Product Code: BKM 120
Pharmaceutical Form: Capsule, hard
Current Sponsor code: BKM120
Other descriptive name: BKM120
Concentration unit: mg milligram(s)
Concentr
Sponsors
SOLTI (Grupo Español de Estudio, Tratamiento y Otras Estrategias Experimentales en Tumores Sólidos)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject has pathologically and radiologically confirmed metastatic triple negative breast cancer (Stage IV disease), previously documented by histological analysis, which is ER-negative and PR-negative by immunohistochemistry (IHC) defined as ER and PR expression =65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1.Patient has received previous treatment with PI3K inhibitors. 2.Patient has symptomatic CNS metastases 3.Patients with controlled and asymptomatic CNS metastases may participate.The patient must have completed any prior treatment for CNS metastases > 28 days prior to enrollment. Patients with previously treated brain metastases on a stable low dose corticosteroids treatment are eligible 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). An exception to this rule are patients with documented germline mutations in BRCA1 or 2, who may have previous history of cancer. 5.Patient has any of the following mood disorders, 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 in 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 ?? CTCAE grade 3 anxiety 6.Patient is concurrently using other approved or investigational antineoplastic agent 7.Patient has received 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: ?LVEF 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 ?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 (NYHAclass 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 13.Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 14.Patient receiving chronic treatment with steroids or another immunosuppressive agent. Note: Topical applications, inhaled sprays, eye drops or local injections are allowed. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment (e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment, are eligible. 15.Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator?s judgment contraindicate her participa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine clinical activity of BKM120 in patients with metastatic triple negative breast cancer that have developed disease progression after standard chemotherapy in the adjuvant or metastatic setting.;Primary end point(s): Rate of clinical benefit = CR + PR + SD for ?4 months) per RECIST 1.1;Secondary Objective: - To determine Progression Free Survival (PFS) - To determine Overall Survival(OS) - To characterize the Safety - To determine molecular alterations in tumor tissue that correlate with clinical activity of BKM120 in TNBC - To determine if pre-selection of patients depending on specific tumor molecular alterations can increase the probability of a clinical response to BKM120 - To assess the pharmacodynamic (PD) effect of BKM120, measured by the impact of the drug on various biomarkers in a well defined population (TNBC).;Timepoint(s) of evaluation of this end point: -A preliminary analysis of the main efficacy and safety data will be performed using the cut-off date that is defined 16 weeks after the first dose of the 29th patient treated in the study (time for 2 post-baseline evaluations and confirmation of response) -The molecular analysis will be performed using the cut-off date that is defined 16 weeks after the first dose of the 50th patient treated in the study (time for 2 post-baseline evaluations and confirmation of response) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? PFS per RECIST 1.1 ? Time from randomization until death from any cause ? Frequency and Severity of Adverse Events ? Tumor molecular analysis of including, but not limited to: PTEN, INPP4B pAkt S473, pS6, and pMAPK by IHC, and PIK3CA mutations on exons 9 and 20. ? Gene expression profile by DNA microarray. ? Correlation analysis between molecular alterations and clinical benefit ? Rate of clinical benefit = CR + PR + SD for ?4 months) per RECIST 1.1 after preselection. ? Change from baseline in Gene expression assessment and levels of p-AKT and S6 in tumors and glucose metabolism markers: e.g., glucose, insulin & C-peptide in blood;Timepoint(s) of evaluation of this end point: The molecular analysis will be performed using the cut-off date that is defined 16 weeks after the first dose of the 50th patient treated in the study (time for 2 post-baseline evaluations and confirmation of response) Final statistical analysis will be done after completion of the entire study | — |
Countries
Spain
Contacts
Public ContactClinical Research Organisation
Recerca Clinica, S.L
Outcome results
None listed