A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02273973
• Date of registration: 22/10/2014
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)
• Scientific title: A Phase II Randomized, Double-Blind Study of Neoadjuvant Letrozole Plus GDC-0032 Versus Letrozole Plus Placebo in Postmenopausal Women With ER-positive/HER2-negative, Early Stage Breast Cancer
• Date of first enrolment: November 12, 2014
• Target sample size: 334
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02273973
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Belgium, Brazil, Chile, Czech Republic, Czechia, El Salvador, France, Germany, Guatemala, Hungary, Italy, Korea, Republic of, Mexico, Panama, Peru, Poland, Portugal, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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 (
- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Letrozole

Drug: Taselisib

Other: Placebo

Primary Outcome(s)

Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 [Time Frame: From Baseline to 16 weeks]

Secondary Outcome(s)

Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants [Time Frame: From Baseline to 16 weeks]

Central Assessments of Changes in Ki67 Levels [Time Frame: From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18)]

Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30) [Time Frame: Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery]

Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With Adverse Events [Time Frame: Baseline up to 22 weeks]

Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants [Time Frame: From Baseline to 16 weeks]

Preoperative Endocrine Prognostic Index (PEPI ) Score [Time Frame: Week 16]

Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants [Time Frame: From Baseline to 16 weeks]

Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants [Time Frame: From Baseline to 16 weeks]

Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23) [Time Frame: Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery]

Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI [Time Frame: From Baseline to Surgery (Weeks 17-18)]

Secondary ID(s)

GO28888

2013-000568-28

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Breast International Group

Austrian Breast and Colorectal Cancer Group

SOLTI Breast Cancer Research Group

Results

• Results available: Yes
• Date Posted: 21/05/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02273973