ABCSG 40 Details

A phase II randomized, double-blind placebo controlled, study of letrozole with or without BYL719, for the neoadjuvant treatment of postmenopausal women with hormonereceptor-positive HER2-negative breast cancer

Start:
09/2013, national: 07/2014
Sample size:
320 (international); 40 (national)
Randomizing:
open

Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design

Design ABCSG-40

Click to enlarge

Primary objectives:

To assess the anti-tumor activity of BYL719 once a day plus letrozole once a day plus letrozole versus letrozole alone in increasing the pathologic complete response (pCR) rate during neo-adjuvant treatment among postmenopausal patients with HR+, HER2-negative breast cancer for each of the two cohorts: i) PIK3CA mutated and ii) PIK3CA wild type tumors and assessment of the anti-tumor activity in increasing the objective response rate (ORR).

Secondary objectives:

  • To evaluate the objective response rate (RR, complete + partial) for each of the two cohorts, namely, i) PIK3CA mutated and ii) PIK3CA wild type
  • To evaluate the safety and tolerability of the drug combinations for each of the two cohorts, namely, i) PIK3CA mutated and ii) PIK3CA wild type
  • To estimate the rate of breast conserving surgery for each of the two cohorts, namely, i) PIK3CA mutated and ii) PIK3CA wild type
  • To evaluate the association between changes in Ki67 from baseline to day 15, and baseline to surgery, with pCR for each of the two cohorts, namely, i) PIK3CA mutated and ii) PIK3CA wild type
  • To assess preoperative endocrine prognostic index (PEPI) score for each of the two cohorts, namely, i) PIK3CA mutated and ii) PIK3CA wild type
  • To characterize the pharmacokinetics of BYL719 and letrozole when given in combination

Inclusion criteria:

  1. Patient has T2-T3, any N, M0, operable breast cancer
  2. Patients must have measurable tumor
  3. Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
  4. Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
  5. 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
  6. 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)
  7. Patient has Ki67 level status determined centrally
  8. Patient has an Eastern Cooperative Oncology Group (ECOG)≤ 1 which the investigator believes is stable at the time of screening

Exclusion criteria:

  1. Patient has locally recurrent or metastatic disease
  2. Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before study entry.
  3. Patient with clinically manifest diabetes mellitus (fasting glucose > 120 mg/dl or 6.7 mmol/L), or documented steroid induced diabetes mellitus
  4. Patient has a score ≥ 12 on the PHQ-9 questionnaire
  5. 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)
  6. Patient has a GAD-7 mood scale score ≥ 15
  7. 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.
  8. Patient has ≥ CTCAE grade 3 anxiety