A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Letrozole; Placebo; Taselisib
Intervention description: Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.; Placebo tablets matched to taselisib formulation will be administered orally daily on 5 days-on/2 days-off schedule for up to 16 weeks.; Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.
Intervention MeSH terms: Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 334.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the
      effect of combining letrozole and GDC-0032 (also known as taselisib) versus letrozole and
      placebo in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth
      factor receptor 2 (HER2) untreated, Stage I-III operable breast cancer. Participants will be
      randomized into one of the two treatment arms with a 1:1 randomization ratio. Letrozole at
      2.5 milligrams (mg) will be dosed once daily plus either Taselisib at 4 mg (two 2-mg tablets)
      or placebo on a 5 days-on/ 2 days-off schedule for a total of 16 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female participants

          -  Postmenopausal status

          -  Histologically confirmed invasive breast carcinoma, with all of the following
             characteristics: (i) Primary tumor greater than or equal to (>/=) 2 centimeters (cm)
             in largest diameter (cT1-3) by MRI; (ii) Stage I to operable Stage III breast cancer;
             (iii) Documented absence of distant metastases (M0)

          -  Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative
             (HER2-) breast cancer

          -  Breast cancer eligible for primary surgery

          -  Tumor tissue from formalin-fixed paraffin-embedded cores (FFPE) core biopsy of breast
             primary tumor that is confirmed as evaluable for phosphatidylinositol-4,5-bisphosphate
             3-kinase, catalytic subunit alpha (PIK3CA) mutation status by central histopathology
             laboratory

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Fasting glucose less than or equal to (</=) 125 milligrams per deciliter (mg/dL)

          -  Adequate hematological, renal, and hepatic function

          -  Absence of any psychological, familial, sociological, or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule

          -  Ability and willingness to comply with study visits, treatment, testing, and to comply
             with the protocol, in the investigator's judgment

        Exclusion Criteria:

          -  Any prior treatment for primary invasive breast cancer

          -  Participants with cT4 or cN3 stage breast tumors

          -  Bilateral invasive, multicentric, or metastatic breast cancer

          -  Participants who have undergone excisional biopsy of primary tumor and/or axillary
             lymph nodes or sentinel lymph node biopsy

          -  Type 1 or 2 diabetes requiring antihyperglycemic medication

          -  Inability or unwillingness to swallow pills

          -  Malabsorption syndrome or other condition that would interfere with enteric absorption

          -  History of prior or currently active small or large intestine inflammation (such as
             Crohn's disease or ulcerative colitis). Any predisposition for gastrointestinal (GI)
             toxicity requires prior approval from the Medical Monitor.

          -  Congenital long QT syndrome or QT interval corrected using Fridericia's formula (QTcF)
             >470 milliseconds (msec)

          -  Diffusing capacity of the lungs for carbon monoxide (DLCO) <60% of the predicted
             values

          -  Clinically significant (i.e., active) cardiovascular disease, uncontrolled
             hypertension, unstable angina, history of myocardial infarction, cardiac failure class
             II-IV

          -  Any contraindication to MRI examination

          -  Active infection requiring intravenous antibiotics

          -  Participants requiring any daily supplemental oxygen

          -  Clinically significant history of liver disease, including viral or other known
             hepatitis, current alcohol abuse, or cirrhosis

          -  Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic
             dysfunction, physical examination finding, or clinical laboratory finding giving
             reasonable suspicion of a disease or condition that contraindicates the use of an
             investigational drug, that may affect the interpretation of the results, or renders
             the participants at high risk from treatment complications

          -  Significant traumatic injury within 3 weeks prior to initiation of study treatment

          -  Major surgical procedure within 4 weeks prior to initiation of study treatment

          -  Inability to comply with study and follow-up procedures

          -  History of other malignancy within 5 years prior to screening, except for
             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or
             Stage I uterine cancer