Clinical Trials /

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

NCT02273973

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: GO28888
  • SECONDARY ID: 2013-000568-28
  • NCT ID: NCT02273973

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleLetrozole + Placebo
TaselisibGDC-0032Letrozole + Taselisib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Letrozole + PlaceboPlacebo ComparatorParticipants will receive 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
  • Letrozole
Letrozole + TaselisibExperimentalParticipants will receive 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.
  • Letrozole
  • Taselisib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) via Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With OR by Centrally Assessed Breast MRI via mRECIST in PIK3CA Wildtype (WT) Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer Staging System in PIK3CA WT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With OR by Breast Ultrasound via mRECIST in PIK3CA MT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With OR by Breast Ultrasound via mRECIST in PIK3CA WT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With OR by Mammography via mRECIST in PIK3CA MT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With OR by Mammography via mRECIST in PIK3CA WT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With OR by Clinical Breast Exam (Palpation) via mRECIST in PIK3CA MT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure:Percentage of Participants With OR by Clinical Breast Exam (Palpation) via mRECIST in PIK3CA WT Participants
Time Frame:From Baseline to 16 weeks
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Preoperative Endocrine Prognostic Index (PEPI) Score
Time Frame:Week 16
Safety Issue:
Description:
Measure:Changes in Enhancing Tumor Volume as Measured by Breast MRI
Time Frame:From Baseline to Surgery (Weeks 17-18)
Safety Issue:
Description:
Measure: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 (surgery will be performed on Weeks 17-18)
Safety Issue:
Description:
Measure: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 (surgery will be performed on Weeks 17-18)
Safety Issue:
Description:
Measure:Percentage of Participants With Adverse Events
Time Frame:Baseline up to 22 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Genentech, Inc.

Last Updated

September 22, 2017