A phase II randomized, double-blind placebo controlled, study of letrozole with or without BYL719 or buparlisib, for the neoadjuvant treatment of postmenopausal women with hormone receptor-positive HER2-negative breast cancer.
- Conditions
- neoadjuvant hormone-receptor positive HER2-negative breast cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001862-41-ES
- Lead Sponsor
- ovartis Farmacéutica , S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 372
- Patient has T2-T3, any N, M0, operable breast cancer.
- Patients must have measurable tumor.
- Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
- Patient has estrogen-receptor and/or progesterone positive breast cancer as
per local laboratory testing.
Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing.
- Patient has known PIK3CA mutation status (mutated or wild-type) as defined
by a Novartis designated laboratory. (Patients with unknown PIK3CA mutation
status will not be enrolled).
- Patient has Ki67 level status determined centrally.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance
status ? 1 which the investigator believes is stable at the time of screening.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 72
- Patient has locally recurrent or metastatic disease.
- Patient has received any systemic therapy (e.g. chemotherapy, targeted
therapy, immunotherapy) or radiotherapy for current breast cancer disease
before study entry.
- Patient with clinically manifest diabetes mellitus (fasting glucose > 120 mg/dl
or 6.7 mmol/L), or documented steroid induced diabetes mellitus.
- Patient has a score ? 12 on the PHQ-9 questionnaire.
- Patient selects a response of ?1, 2 or 3? to question number 9 on the PHQ-9
questionnaire regarding potential for suicidal thoughts or ideation (independent
of the total score of the PHQ-9).
- Patient has a GAD-7 mood scale score ? 15.
- Patient has a 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
(e.g. risk of doing harm to self or others), or with an active severe personality
disorder (defined according to DSM- IV). Note: for patients with psychotropic
treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
- Patient has ? CTCAE grade 3 anxiety.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the anti-tumor activity of BYL719 QD plus letrozole and buparlisib QD plus letrozole versus letrozole alone in increasing the pathologic complete response (pCR) rate during neo-adjuvant treatment for each of the two groups: i) PIK3CA mutated and ii) PIK3CA wild tumor types.;Secondary Objective: - objective response rate (RR, complete + partial) for each of the 2 groups, namely i) PIK3CA mutated and ii) PIK3CA wild tumor types.<br>-- safety and tolerability of the combinations for each of the two groups...<br>--estimate rate of breast conserving surgery;Primary end point(s): Pathologic complete response;Timepoint(s) of evaluation of this end point: following 24 weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): --ORR<br>--safety & tolerability<br>--breast conserving surgery<br>--changes in Ki67<br>--assessment of PEPI score<br>--PK for buparlisib/BYL719 and letrozole;Timepoint(s) of evaluation of this end point: Along the trial