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

This study has been completed.
Sponsor:
Collaborators:
SOLTI Breast Cancer Research Group
Breast International Group
Austrian Breast and Colorectal Cancer Group
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02273973
First received: October 22, 2014
Last updated: August 3, 2017
Last verified: August 2017
  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.

Condition Intervention Phase
Breast Cancer Drug: Letrozole Other: Placebo Drug: Taselisib Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • 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 ]
  • 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 Staging System [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Centrally Assessed Breast MRI via mRECIST in 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 American Joint Committee on Cancer Staging System in PIK3CA MT Participants [ Time Frame: From Baseline to 16 weeks ]

Secondary Outcome Measures:
  • Percentage of Participants With OR by Centrally Assessed Breast MRI via mRECIST in PIK3CA Wildtype (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 American Joint Committee on Cancer Staging System in PIK3CA WT Participants [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Breast Ultrasound via mRECIST in PIK3CA MT Participants [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Breast Ultrasound via mRECIST in PIK3CA WT Participants [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Mammography via mRECIST in PIK3CA MT Participants [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Mammography via mRECIST in PIK3CA WT Participants [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Clinical Breast Exam (Palpation) via mRECIST in PIK3CA MT Participants [ Time Frame: From Baseline to 16 weeks ]
  • Percentage of Participants With OR by Clinical Breast Exam (Palpation) via mRECIST in PIK3CA WT 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) ]
  • Preoperative Endocrine Prognostic Index (PEPI) Score [ Time Frame: Week 16 ]
  • Changes in Enhancing Tumor Volume as Measured by Breast MRI [ Time Frame: From Baseline 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 (surgery will be performed on Weeks 17-18) ]
  • 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) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 22 weeks ]

Enrollment: 330
Actual Study Start Date: November 12, 2014
Study Completion Date: March 13, 2017
Primary Completion Date: March 13, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Letrozole + Placebo
Participants 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.
Drug: Letrozole
Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.
Other: Placebo
Placebo tablets matched to taselisib formulation will be administered orally daily on 5 days-on/2 days-off schedule for up to 16 weeks.
Experimental: Letrozole + Taselisib
Participants 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.
Drug: Letrozole
Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.
Drug: Taselisib
Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.
Other Name: GDC-0032

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02273973

  Show 117 Study Locations
Sponsors and Collaborators
Genentech, Inc.
SOLTI Breast Cancer Research Group
Breast International Group
Austrian Breast and Colorectal Cancer Group
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02273973     History of Changes
Other Study ID Numbers: GO28888
2013-000568-28 ( EudraCT Number )
Study First Received: October 22, 2014
Last Updated: August 3, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 23, 2017