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

Breast Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02273973
• Other study ID #: GO28888
• Secondary ID: 2013-000568-28
• Status: Completed
• Phase: Phase 2
• Start date: November 12, 2014
• Est. completion date: March 13, 2017

Study information

• Verified date: April 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: March 13, 2017
• Est. primary completion date: March 13, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Drug:
• Taselisib
Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.

Locations

Country	Name	City	State
Australia	Kinghorn Cancer Centre; St Vincents Hospital	Darlinghurst	New South Wales
Australia	Victorian Breast and Oncology Care	East Melbourne	Victoria
Australia	Cabrini Medical Centre; Oncology	Malvern	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Newcastle Mater Misericordiae Hospital; Oncology	Waratah	New South Wales
Austria	Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie	Graz
Austria	LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie	Graz
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie	Innsbruck
Austria	Ordensklinikum Linz Barmherzige Schwestern ; Abt. f. Allgemein- und Viszeralchirurgie	Linz
Austria	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg
Austria	Brustzentrum - Ordination Dr. Wette	St. Veit/Glan
Austria	Klinikum Kreuzschwestern Wels; Iii. Interne Abt.	Wels
Austria	Krankenhaus Der Stadt Wien-Hietzing; Abt. Für Gynäkologie U. Geburtshilfe	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Chirurgie - Abt. für Allgemeinchirurgie	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie	Wien
Belgium	Institut Jules Bordet	Brussels
Belgium	CHU Brugmann (Victor Horta)	Bruxelles
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	Clinique Ste-Elisabeth	Namur
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Clinica de Neoplasias Litoral	Itajai	SC
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	Instituto Brasileiro De Controle Do Câncer - IBCC; Laboratório De Patologia	São Paulo	SP
Chile	Hospital Clinico Vina del Mar	Viña del Mar
Czechia	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	MULTISCAN, s.r.o., Radiologicke centrum Pardubice	Pardubice
Czechia	Oblastni nemocnice Pribram	Pribram
El Salvador	Hospital Oncologia; Oncology	Salvador
France	Centre Jean Perrin; Division De Recherche Clinique	Clermont Ferrand
France	Centre Jean Bernard	Le Mans
France	Hopital Saint Louis; Service Onco Thoracique	Paris
France	Institut Curie; Oncologie Medicale	Paris
France	Centre Rene Huguenin; ONCOLOGIE GENETIQUE	Saint Cloud
France	CHI de Toulon - Hôpital Sainte Musse	Toulon
France	Institut de Cancérologie de Lorraine	Vandoeuvre-Les-Nancy
Germany	Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)	Berlin
Germany	Studienzentrum Berlin City	Berlin
Germany	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld
Germany	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden
Germany	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen
Germany	Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum	Gelsenkirchen
Germany	Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie	Hamburg
Germany	Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe	Hannover
Germany	Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe	Lübeck
Germany	Rotkreuzklinikum München; Frauenklinik	Muenchen
Germany	Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe	Münster
Germany	Universitätsklinikum Ulm Am Michelsberg; Frauenklinik	Ulm
Germany	Marien-Hospital Witten; Frauenklinik Brustzentrum	Witten
Guatemala	Centro Oncológico Sixtino / Centro Oncológico SA	Guatemala
Guatemala	Grupo Angeles	Guatemala City
Hungary	Szent Margit Hospital; Dept. of Oncology	Budapest
Hungary	Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika	Debrecen
Hungary	Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont	Kecskemet
Hungary	B-A-Z County Hospital	Miskolc
Hungary	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	ASST DI CREMONA; Dip. Medicina - S.C. Oncologia	Cremona	Lombardia
Italy	Uni Degli Studi Di Genova ; Clinica Di Medicina Interna Ad Indirizzo Oncologico	Genova	Liguria
Italy	Ospedale Per Acuti Mater Salutis Di Legnago	Legnago	Lombardia
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica	Milano	Lombardia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	Ospedale degli Infermi	Rimini	Emilia-Romagna
Korea, Republic of	National Cancer Center; Medical Oncology	Gyeonggi-do
Korea, Republic of	Samsung Medical Centre; Division of Hematology/Oncology	Seoul
Korea, Republic of	Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology	Seoul
Korea, Republic of	Yonsei University Severance Hospital; Medical Oncology	Seoul
Mexico	Centro Estatal de Cancerología	Chihuahua
Mexico	Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios	Distrito Federal
Mexico	Consultorio de Medicina Especializada; Dentro de Condominio San Francisco	Mexico City
Panama	Centro Oncologico America	Panama
Peru	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima
Peru	Hospital Nacional Cayetano Heredia; Hematology - Oncology	Lima
Peru	Oncosalud Sac; Oncología	Lima
Poland	Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk
Poland	Wojewódzki Szpital Specjalistyczny im. M. Kopernika; Oddzial Chemioterapii	Lodz
Poland	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii	Otwock
Poland	Wielkopolskie Centrum Onkologii; im. Marii Sklodowskiej-Curie	Poznan
Poland	Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon	Warszawa
Portugal	Centro Clinico Champalimaud; Oncologia Medica	Lisboa
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	Instituto Universitario Dexeus; Servicio de Oncología	Barcelona
Spain	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia	Girona
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario de Fuenlabrada; Servicio de Oncologia	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Fundación IVO	Valencia
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia
Spain	Hospital Clinico Universitario; Oncologia	Valencia
Switzerland	Kantonsspital Baden; Frauenklinik	Baden
Switzerland	Kantonsspital Graubünden;Onkologie und Hämatologie	Chur
Switzerland	Fondazione Oncologia Lago Maggiore	Locarno
United Kingdom	Royal Bournemouth General Hospital; Oncology	Bournemouth
United Kingdom	Frimley Park Hospital; Breast Resaerch Team	Camberley
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Christie Hospital	Manchester
United States	MSKCC at Basking Ridge	Basking Ridge	New Jersey
United States	MGH Cancer Center	Boston	Massachusetts
United States	MSKCC @ Commack	Commack	New York
United States	MSKCC @ West Harrison	Harrison	New York
United States	MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan-Kettering Cancer Center; Hematology/Oncology	New York	New York
United States	MSKC @ Rockville	Rockville Centre	New York
United States	Breastlink Med Group Inc	Santa Ana	California

Sponsors (4)

Lead Sponsor	Collaborator
Genentech, Inc.	Austrian Breast and Colorectal Cancer Group, Breast International Group, SOLTI Breast Cancer Research Group

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate (ORR) was defined as proportion of participants achieving complete response (CR) or partial response (PR). As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Primary	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	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).	From Baseline to 16 weeks
Primary	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	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Primary	Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Secondary	Central Assessments of Changes in Ki67 Levels	Ki67 is a prognostic marker and is used to evaluate the proliferative activity of breast cancer.	From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18)
Secondary	Preoperative Endocrine Prognostic Index (PEPI ) Score	To obtain the PEPI score, risk points for relapse-free survival (RFS) and breast cancer-specific survival (BCSS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each participant is the sum of the risk points derived from the primary tumor (pT) stage, regional lymph nodes (pN) stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each participant is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).	Week 16
Secondary	Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI		From Baseline to Surgery (Weeks 17-18)
Secondary	Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30)	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). The last 2 questions represented the participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement. Here, Post surgery= PS.	Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery
Secondary	Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23)	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. Here, Post surgery= PS.	Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery
Secondary	Percentage of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline up to 22 weeks