CBKM120ZES02T/SOLTI-1103

SOLTI

C/ Balmes 89 3-7, Barcelona, Spain, 08008

Investigación Clínica, SOLTI, +34 933436302, regsolti@gruposolti.org

Investigación Clínica, SOLTI, +34 933436302, regsolti@gruposolti.org

No

No

No

Final

30 Sep 2015

Yes

30 Sep 2015

Yes

30 Sep 2015

No

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.

All patients were screened for inclusion and exclusion criteria within 2 weeks prior to the first dose of BKM120. Screening includes obtaining written informed consent, a physical exam, demography, medical history/current medical conditions, current concomitant medications/therapies, disease history and extent of disease, and prior anticancer therapies. Additionally, the following assessments were performed: Physical examination, weight and height; Vital signs including sitting blood pressure/pulse and heart rate, respiratory rate and temperature; ECOG performance status; ECG; Safety laboratory assessments: chemistry, hematology and urinalysis; Pregnancy test; Neuro-psychiatric assessment (self-rating mood questionnaire); - Baseline TAC or MRI;Baseline tumour tissue collection for biomarker assessments. Patients continued on treatment with BKM120 until the patient experiences unacceptable toxicity that recludes any further treatment, disease progression, and/or treatment was discontinued at the discretion of the investigator or by patient refusal. A treatment cycle was arbitrarily defined as 28 days for the purposes of scheduling procedures and evaluations. On Day 1 and 15 of each cycle, the following assessments were performed: Complete physical examination; ECOG performance status; Vital signs; Body weight; Collection of any AEs and SAEs, with assignment of the appropriate AE grade according to NCI CTCAE v.4.0; Documentation of concomitant medications; Laboratory tests ( haematology tests (with differential, reticulocytes, and platelets count), coagulation panel (including INR and APTT), and comprehensive chemistry panel (sodium, potassium, chloride, creatinine, calcium, BUN, albumin, AST, ALT, AP, LDH, and total bilirubin);fasting plasma glucose); ECG. Additionally, Neuro-psychiatric assessment (self-rating mood questionnaire) was done on day 15 and every 2 weeks. Response assessment at the end of C2 and every 2 cycles.

26 Jun 2012

No

Yes

Spain: 23

United States: 27

50

23

0

0

0

0

0

0

50

0

0

Stage I (overall period)

Not applicable

BKM 120

AN2025 BKM120 PI3K_Inhibitor_BKM120

Capsule

Oral use

The investigational study drug used in this trial was BKM120, supplied as 10-mg and 50- mg hard gelatine capsules. The dose of 100 mg/day was identified as the maximum tolerated dose (MTD) in the phase I study [BKM120X2101]. BKM120 was administered on a continuous once daily dosing schedule at a dose of 100 mg (p.o). The patient was dosed on a flat scale of 100mg/day and the dose of the drug wasn’t adjusted to body weight or body surface area.

Stage I

Cohort 1 (unselected)

Efficacy endpoint

All recruited population that receives the study treatment. This population was the primary population for all efficacy parameters. Fifty women were enrolled between June 2012 and September 2014 across 4 sites in Spain and 1 site in USA, with a median follow-up of 13.8 months. Evaluable patients for tumor response were all treated patients with at least one baseline tumor assessment and one post-baseline assessment, and also all treated patients with early disease progression (PD) before first planned tumor assessment.

Safety population

A subset of randomized patients who received at least one cycle of treatment. This population was used for the safety analysis.

The primary efficacy endpoint was rate of clinical benefit (CR+PR+SD≥4 months) per RECISTS 1.1. At interim analysis, 4 (13%) patients had stable disease. 37 patients were evaluable for best response; 12 patients were taken off treatment before the first restaging evaluation due to clinical progression, and one patient was taken off treatment due to toxicity. No patient had confirmed CR or PR. Six patients (12%) experienced stable disease > 4 months, and met the study pre-defined primary endpoint of clinical benefit. The rate of clinical benefit was 12% (95% CI 5.6-23.8%).

Primary

The baseline evaluation performed within 28 days prior to enrollment. During treatment, every 2 cycles and in 7 days from the planned date. At the end of the study it is recommended f it has not been done in the previous 21 days.

Secondary

from date of study enrollment until disease progression or death from any cause, whichever came first. If no PFS events were observed, patients’ PFS times were censored at the date of their last assessments

Secondary

OS was defined as time from date of study enrollment until death from any cause. For patients alive, their OS times were censored at the date of last known alive.

Adverse events (AEs) were assessed according to the National Cancer Institute CTCAE version 4.0. Safety assessments, including fasting plasma glucose, were conducted every 2 weeks for the first 2 cycles

Two different mood questionnaires (PHQ-9 and GAD-7) must be completed at each assessment visit to the clinic, as well as at the end-of-treatment visit.

21.1

Cohort 1