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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02273973




Registration number
NCT02273973
Ethics application status
Date submitted
22/10/2014
Date registered
24/10/2014
Date last updated
21/05/2018

Titles & IDs
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
Secondary ID [1] 0 0
2013-000568-28
Secondary ID [2] 0 0
GO28888
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Letrozole
Other interventions - Placebo
Treatment: Drugs - Taselisib

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.

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.


Treatment: Drugs: Letrozole
Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.

Other interventions: 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.

Treatment: Drugs: Taselisib
Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
From Baseline to 16 weeks
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
From Baseline to 16 weeks
Primary outcome [3] 0 0
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
Timepoint [3] 0 0
From Baseline to 16 weeks
Primary outcome [4] 0 0
Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants
Timepoint [4] 0 0
From Baseline to 16 weeks
Secondary outcome [1] 0 0
Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants
Timepoint [1] 0 0
From Baseline to 16 weeks
Secondary outcome [2] 0 0
Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants
Timepoint [2] 0 0
From Baseline to 16 weeks
Secondary outcome [3] 0 0
Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants
Timepoint [3] 0 0
From Baseline to 16 weeks
Secondary outcome [4] 0 0
Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants
Timepoint [4] 0 0
From Baseline to 16 weeks
Secondary outcome [5] 0 0
Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants
Timepoint [5] 0 0
From Baseline to 16 weeks
Secondary outcome [6] 0 0
Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants
Timepoint [6] 0 0
From Baseline to 16 weeks
Secondary outcome [7] 0 0
Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants
Timepoint [7] 0 0
From Baseline to 16 weeks
Secondary outcome [8] 0 0
Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants
Timepoint [8] 0 0
From Baseline to 16 weeks
Secondary outcome [9] 0 0
Central Assessments of Changes in Ki67 Levels
Timepoint [9] 0 0
From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18)
Secondary outcome [10] 0 0
Preoperative Endocrine Prognostic Index (PEPI ) Score
Timepoint [10] 0 0
Week 16
Secondary outcome [11] 0 0
Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI
Timepoint [11] 0 0
From Baseline to Surgery (Weeks 17-18)
Secondary outcome [12] 0 0
Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30)
Timepoint [12] 0 0
Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery
Secondary outcome [13] 0 0
Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23)
Timepoint [13] 0 0
Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery
Secondary outcome [14] 0 0
Percentage of Participants With Adverse Events
Timepoint [14] 0 0
Baseline up to 22 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/03/2017
Sample size
Target
Accrual to date
Final
334
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Newcastle Mater Misericordiae Hospital; Oncology - Waratah
Recruitment hospital [3] 0 0
Victorian Breast and Oncology Care - East Melbourne
Recruitment hospital [4] 0 0
Cabrini Medical Centre; Oncology - Malvern
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
- East Melbourne
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Austria
State/province [6] 0 0
Graz
Country [7] 0 0
Austria
State/province [7] 0 0
Innsbruck
Country [8] 0 0
Austria
State/province [8] 0 0
Linz
Country [9] 0 0
Austria
State/province [9] 0 0
Salzburg
Country [10] 0 0
Austria
State/province [10] 0 0
St. Veit/Glan
Country [11] 0 0
Austria
State/province [11] 0 0
Wels
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
Belgium
State/province [14] 0 0
Bruxelles
Country [15] 0 0
Belgium
State/province [15] 0 0
Edegem
Country [16] 0 0
Belgium
State/province [16] 0 0
Namur
Country [17] 0 0
Brazil
State/province [17] 0 0
RS
Country [18] 0 0
Brazil
State/province [18] 0 0
SC
Country [19] 0 0
Brazil
State/province [19] 0 0
SP
Country [20] 0 0
Chile
State/province [20] 0 0
Viña del Mar
Country [21] 0 0
Czechia
State/province [21] 0 0
Hradec Kralove
Country [22] 0 0
Czechia
State/province [22] 0 0
Olomouc
Country [23] 0 0
Czechia
State/province [23] 0 0
Pardubice
Country [24] 0 0
Czechia
State/province [24] 0 0
Pribram
Country [25] 0 0
El Salvador
State/province [25] 0 0
Salvador
Country [26] 0 0
France
State/province [26] 0 0
Clermont Ferrand
Country [27] 0 0
France
State/province [27] 0 0
Le Mans
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Saint Cloud
Country [30] 0 0
France
State/province [30] 0 0
Toulon
Country [31] 0 0
France
State/province [31] 0 0
Vandoeuvre-Les-Nancy
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Bielefeld
Country [34] 0 0
Germany
State/province [34] 0 0
Dresden
Country [35] 0 0
Germany
State/province [35] 0 0
Essen
Country [36] 0 0
Germany
State/province [36] 0 0
Gelsenkirchen
Country [37] 0 0
Germany
State/province [37] 0 0
Hamburg
Country [38] 0 0
Germany
State/province [38] 0 0
Hannover
Country [39] 0 0
Germany
State/province [39] 0 0
Lübeck
Country [40] 0 0
Germany
State/province [40] 0 0
Muenchen
Country [41] 0 0
Germany
State/province [41] 0 0
Münster
Country [42] 0 0
Germany
State/province [42] 0 0
Ulm
Country [43] 0 0
Germany
State/province [43] 0 0
Witten
Country [44] 0 0
Guatemala
State/province [44] 0 0
Guatemala City
Country [45] 0 0
Guatemala
State/province [45] 0 0
Guatemala
Country [46] 0 0
Hungary
State/province [46] 0 0
Budapest
Country [47] 0 0
Hungary
State/province [47] 0 0
Debrecen
Country [48] 0 0
Hungary
State/province [48] 0 0
Kecskemet
Country [49] 0 0
Hungary
State/province [49] 0 0
Miskolc
Country [50] 0 0
Hungary
State/province [50] 0 0
Szeged
Country [51] 0 0
Italy
State/province [51] 0 0
Emilia-Romagna
Country [52] 0 0
Italy
State/province [52] 0 0
Liguria
Country [53] 0 0
Italy
State/province [53] 0 0
Lombardia
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Gyeonggi-do
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Seoul
Country [56] 0 0
Mexico
State/province [56] 0 0
Chihuahua
Country [57] 0 0
Mexico
State/province [57] 0 0
Distrito Federal
Country [58] 0 0
Mexico
State/province [58] 0 0
Mexico City
Country [59] 0 0
Panama
State/province [59] 0 0
Panama
Country [60] 0 0
Peru
State/province [60] 0 0
Lima
Country [61] 0 0
Poland
State/province [61] 0 0
Bydgoszcz
Country [62] 0 0
Poland
State/province [62] 0 0
Gdansk
Country [63] 0 0
Poland
State/province [63] 0 0
Lodz
Country [64] 0 0
Poland
State/province [64] 0 0
Otwock
Country [65] 0 0
Poland
State/province [65] 0 0
Poznan
Country [66] 0 0
Poland
State/province [66] 0 0
Warszawa
Country [67] 0 0
Portugal
State/province [67] 0 0
Lisboa
Country [68] 0 0
Portugal
State/province [68] 0 0
Porto
Country [69] 0 0
Spain
State/province [69] 0 0
Cordoba
Country [70] 0 0
Spain
State/province [70] 0 0
LA Coruña
Country [71] 0 0
Spain
State/province [71] 0 0
Barcelona
Country [72] 0 0
Spain
State/province [72] 0 0
Caceres
Country [73] 0 0
Spain
State/province [73] 0 0
Castellon
Country [74] 0 0
Spain
State/province [74] 0 0
Girona
Country [75] 0 0
Spain
State/province [75] 0 0
Jaen
Country [76] 0 0
Spain
State/province [76] 0 0
Lerida
Country [77] 0 0
Spain
State/province [77] 0 0
Madrid
Country [78] 0 0
Spain
State/province [78] 0 0
Sevilla
Country [79] 0 0
Spain
State/province [79] 0 0
Valencia
Country [80] 0 0
Switzerland
State/province [80] 0 0
Baden
Country [81] 0 0
Switzerland
State/province [81] 0 0
Chur
Country [82] 0 0
Switzerland
State/province [82] 0 0
Locarno
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Bournemouth
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Camberley
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Glasgow
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
SOLTI Breast Cancer Research Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Breast International Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Austrian Breast and Colorectal Cancer Group
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02273973
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02273973