Étude pour évaluer l'efficacité et l'innocuité d'Alpelisib Plus Fulvestrant chez des participantes atteintes d'un cancer du sein avancé HR-positif (HR+), HER2-négatif, après traitement avec un inhibiteur de CDK4/6 et un inhibiteur de l'aromatase. (EPIK-B5)
EPIK-B5 : Une étude de phase III, randomisée, en double aveugle, contrôlée par placebo sur l'alpelisib en association avec le fulvestrant chez les hommes et les femmes ménopausées atteints d'un cancer du sein avancé HR-positif, HER2-négatif avec une mutation PIK3CA, qui a progressé le ou après Inhibiteur de l'aromatase et inhibiteur de CDK4/6
The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is a Phase III, randomized, double-blind, placebo-controlled, international, multi-center trial. Men and postmenopausal women will be randomized to either alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant. Randomization will follow a 1:1 randomization ratio and be stratified by presence of lung and/or liver metastases (yes vs. no) and setting at last prior CDK4/6 inhibitor therapy (adjuvant vs metastatic).
Study treatment with alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant will be initiated on Cycle 1 Day 1, and will continue until disease progression per RECIST v1.1 as per BIRC assessment, start of new antineoplastic therapy, death, lost to follow-up, or withdrawal of consent. A cycle is defined as 28 days.
Type d'étude
Inscription (Réel)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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Augsburg, Allemagne, 86150
- Novartis Investigative Site
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Berlin, Allemagne, 13353
- Novartis Investigative Site
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Essen, Allemagne, 45136
- Novartis Investigative Site
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Lübeck, Allemagne, 23538
- Novartis Investigative Site
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North Rhine-Westphalia
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Cologne, North Rhine-Westphalia, Allemagne, 50937
- Novartis Investigative Site
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Brussels, Belgique, 1200
- Novartis Investigative Site
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Brussels, Belgique, 1000
- Novartis Investigative Site
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Ghent, Belgique, 9000
- Novartis Investigative Site
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Leuven, Belgique, 3000
- Novartis Investigative Site
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Liège, Belgique, 4000
- Novartis Investigative Site
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Oost Vlaanderen
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Sint-Niklaas, Oost Vlaanderen, Belgique, 9100
- Novartis Investigative Site
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Plovdiv, Bulgarie, 4004
- Novartis Investigative Site
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Sofia, Bulgarie, 1330
- Novartis Investigative Site
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Alberta
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Calgary, Alberta, Canada, T2N 5G2
- Novartis Investigative Site
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- Novartis Investigative Site
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Aalborg, Danemark, 9000
- Novartis Investigative Site
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A Coruña, Espagne, 15009
- Novartis Investigative Site
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Barcelona, Espagne, 08036
- Novartis Investigative Site
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Madrid, Espagne, 28040
- Novartis Investigative Site
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Málaga, Espagne, 29011
- Novartis Investigative Site
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Zaragoza, Espagne, 50009
- Novartis Investigative Site
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Extremadura
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Badajoz, Extremadura, Espagne, 06080
- Novartis Investigative Site
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Madrid
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Pozuelo de Alarcón, Madrid, Espagne, 28223
- Novartis Investigative Site
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Principality of Asturias
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Oviedo, Principality of Asturias, Espagne, 33011
- Novartis Investigative Site
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Helsinki, Finlande, 00029
- Novartis Investigative Site
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Tampere, Finlande, 33521
- Novartis Investigative Site
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Besançon, France, 25030
- Novartis Investigative Site
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Clermont-Ferrand, France, 63011
- Novartis Investigative Site
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La Roche-sur-Yon, France, 85925
- Novartis Investigative Site
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Lyon, France, 69373
- Novartis Investigative Site
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Marseille, France, 13273
- Novartis Investigative Site
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Montpellier, France, 34298
- Novartis Investigative Site
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Paris, France, 75970
- Novartis Investigative Site
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Paris, France, 75475
- Novartis Investigative Site
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Valenciennes, France, 59300
- Novartis Investigative Site
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Athens, Grèce, 115 22
- Novartis Investigative Site
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Pátrai, Grèce, 265 04
- Novartis Investigative Site
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Budapest, Hongrie, 1122
- Novartis Investigative Site
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Dublin, Irlande, D04 T6F4
- Novartis Investigative Site
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Naples, Italie, 80131
- Novartis Investigative Site
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BA
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Bari, BA, Italie, 70124
- Novartis Investigative Site
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BG
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Bergamo, BG, Italie, 24127
- Novartis Investigative Site
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BO
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Bologna, BO, Italie, 40138
- Novartis Investigative Site
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FI
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Florence, FI, Italie, 50134
- Novartis Investigative Site
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GE
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Genova, GE, Italie, 16132
- Novartis Investigative Site
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MI
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Milan, MI, Italie, 20133
- Novartis Investigative Site
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Milan, MI, Italie, 20141
- Novartis Investigative Site
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Milan, MI, Italie, 20132
- Novartis Investigative Site
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Rozzano, MI, Italie, 20089
- Novartis Investigative Site
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PA
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Palermo, PA, Italie, 90127
- Novartis Investigative Site
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PD
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Padova, PD, Italie, 35128
- Novartis Investigative Site
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PN
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Aviano, PN, Italie, 33081
- Novartis Investigative Site
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RM
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Roma, RM, Italie, 00168
- Novartis Investigative Site
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TR
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Terni, TR, Italie, 05100
- Novartis Investigative Site
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Coimbra, Le Portugal, 3000-075
- Novartis Investigative Site
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Lisbon, Le Portugal, 1400-038
- Novartis Investigative Site
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Lisbon, Le Portugal, 1099-023
- Novartis Investigative Site
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Porto, Le Portugal, 4200-072
- Novartis Investigative Site
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Bydgoszcz, Pologne, 85-796
- Novartis Investigative Site
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Cluj
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Floreşti, Cluj, Roumanie, 407280
- Novartis Investigative Site
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Bratislava, Slovaquie, 812 50
- Novartis Investigative Site
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Bratislava, Slovaquie, 833 10
- Novartis Investigative Site
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Košice, Slovaquie, 041 91
- Novartis Investigative Site
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Brno, Tchéquie, 656 53
- Novartis Investigative Site
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Nový Jičín, Tchéquie, 741 01
- Novartis Investigative Site
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Prague, Tchéquie, 128 08
- Novartis Investigative Site
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Prague, Tchéquie, 100 34
- Novartis Investigative Site
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Prague, Tchéquie, 140 59
- Novartis Investigative Site
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Key Inclusion Criteria:
- Participant is an adult ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.
- Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
- Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.
- Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).
- Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).
- Participant has received ≤ 2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted.
- The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test.
- If female, then the participant must be in postmenopausal status.
Key Exclusion Criteria:
- Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy (ET) per the Investigator's best judgment.
- Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease.
- Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERD), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor.
Other Inclusion and Exclusion Criteria do apply
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Alpelisib plus fulvestrant
Alpelisib 300 mg orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15, and on Day 1 on every Cycle thereafter, in a 28 days cycle. |
Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle. Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days). |
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Comparateur placebo: Alpelisib-matching placebo plus fulvestrant
Alpelisib-matching placebo orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15 and on Day 1 on every Cycle thereafter, in a 28 days cycle. After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded. |
Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days). Alpelisib-matching placebo (tablets) administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle. After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria
Délai: From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.
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Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1. |
From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Overall survival (OS)
Délai: From the date of randomization to the date of death up to a maximum duration of 60 months
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Overall survival (OS) is defined as the time from randomization to the date of death due to any cause |
From the date of randomization to the date of death up to a maximum duration of 60 months
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Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Délai: From the date of randomization up to a maximum duration of 60 months
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Overall response rate (ORR) with confirmed response is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per BIRC and according to RECIST 1.1 |
From the date of randomization up to a maximum duration of 60 months
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Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Délai: From the date of randomization up to a maximum duration of 60 months
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Clinical benefit rate (CBR) with confirmed response is defined as the proportion of participants with a best overall response of confirmed CR or PR, or SD lasting for a duration of at least 24 weeks. CR, PR and SD are defined as per BIRC review according to RECIST 1.1 |
From the date of randomization up to a maximum duration of 60 months
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Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Délai: From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months
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Duration of response (DOR) with confirmed response only applies to participants whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per BIRC review. The start date is the date of first documented response of CR or PR and the end date is defined as the date of the first documented progression or death due to underlying cancer. |
From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months
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Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria
Délai: From the date of randomization to the first documented response up to a maximum duration of 60 months
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Time to response (TTR) is defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed. CR and PR are based on tumor response data as per BIRC review and according to RECIST 1.1 |
From the date of randomization to the first documented response up to a maximum duration of 60 months
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PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status
Délai: From the date of randomization up to a maximum duration of 60 months
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Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1. Results will be presented by PIK3CA mutation status measured in circulating tumor deoxyribonucleic acid (ctDNA) collected at baseline. |
From the date of randomization up to a maximum duration of 60 months
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Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline
Délai: From the date of randomization up to maximum duration of 60 months
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Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline is defined as the time from the date of randomization to the date when ECOG PS has definitively worsened by at least one category compared to baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to the baseline category or better. |
From the date of randomization up to maximum duration of 60 months
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Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)
Délai: From the date of randomization up to maximum duration of 60 months
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Time to definitive (10%) deterioration in global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 is defined as the time from the date of randomization to the date of the first occurrence of at least a 10% worsening from baseline in the global health status/QoL or symptom scale scores, with no subsequent improvement above this threshold during treatment or until death from any cause. The EORTC QLQ-C30 is a validated questionnaire assessing cancer patients' quality of life over the past week, comprising 30 items across 5 functional scales, 3 symptom scales, 6 single items, and a global health status/QoL scale. Scores range from 0 to 100, with higher scores indicating a higher response level. |
From the date of randomization up to maximum duration of 60 months
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Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30
Délai: From the date of randomization up to maximum duration of 60 months
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Change from baseline in global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 refers to the variation in scores from baseline across domain scores, health states, overall health status, and index values at each assessment timepoint. The EORTC QLQ-C30 is a validated questionnaire designed to assess the quality of life of cancer patients over the past week. It includes 30 items comprising 5 functional scales, 3 symptom scales, 6 single items, and a global health status/QoL scale. Each scale and item is scored from 0 to 100, with higher scores indicating a higher response level. |
From the date of randomization up to maximum duration of 60 months
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Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)
Délai: From the date of randomization up to maximum duration of 60 months
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Time from randomization to objective tumor progression on next-line treatment or death from any cause (PFS2) is defined as the time from the date of randomization to the earliest occurrence of either documented disease progression on next-line therapy, as assessed by the investigator, or death from any cause. |
From the date of randomization up to maximum duration of 60 months
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs par site
- Tumeurs
- Maladies de la peau
- Maladies du sein
- Maladies de la peau et du tissu conjonctif
- Tumeurs mammaires
- Hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Composés polycycliques
- Stéroïdes
- Composés à anneau fusionné
- Estradiol
- Estènes
- Origases
- Congénères de l'estradiol
- Hormones stéroïdes gonadiques
- Hormones gonadiques
- Fulvestrant
- Alpelisib
Autres numéros d'identification d'étude
- CBYL719C2303
- 2023-509133-39-00 (Identificateur de registre: CTIS (EU))
- 2023 (Subvention/contrat des NIH des États-Unis)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Informations sur les médicaments et les dispositifs, documents d'étude
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