A phase II trial of BKM120 (a PI3K inhibitor) in patients with triple negative metastatic breast cancer

Phase 1

• Conditions: triple negative metastatic breast cancer; MedDRA version: 14.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-006083-45-ES
• Lead Sponsor: SOLTI (Grupo Español de Estudio, Tratamiento y Otras Estrategias Experimentales en Tumores Sólidos)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-31
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

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 < 1% and HER2 negative by immunohistochemistry (IHC) or FISH/CISH. If patient has more than one histological result, the most recent one has to be considered for inclusion.

2.Subjects must have received at least two prior chemotherapy regimens in the adjuvant or metastatic setting.
3.Availability of a representative tumor specimen (primary or metastasis, archival or fresh) is mandatory at baseline for retrospective analysis of relevant molecular alterations ( e.g., PIK3CA, PTEN, Ras, etc).
4.At least one measurable lesion defined by RECIST 1.1

5.Patient has provided a signed Informed Consent Form (ICF) obtained prior to any screening procedure.
6.Patient is ? 18 years at the day of consenting to the study
7.Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ? 2
8.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 ? 2Potassium, calcium, magnesium within normal limits for the institution
? Serum Creatinine ? 1.5 x ULN
?Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ? 3.0 x ULN if liver metastases are present)
?Serum bilirubin within normal range (or ? 1.5 x ULN if liver metastases are present; or total bilirubin ? 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
? 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 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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 < 50% as determined by MUGA or 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
?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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified