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JOURNAL ONKOLOGIE – STUDIE
EPIK-B5

Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.

Rekrutierend

NCT-Nummer:
NCT05038735

Studienbeginn:
November 2021

Letztes Update:
01.03.2024

Wirkstoff:
Alpelisib, Fulvestrant, Alpelisib-matching placebo

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Novartis Pharmaceuticals

Studienlocations
(3 von 95)

Novartis Investigative Site
86150 Augsburg
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
10117 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
45136 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
50937 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
23538 Luebeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
81377 Muenchen
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
88214 Ravensburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
9100 Sint Niklaas
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
1000 Bruxelles
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
1200 Bruxelles
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
8000 Burgas
BulgariaZurückgezogen» Google-Maps
Novartis Investigative Site
T2N 4N2 Calgary
CanadaRekrutierend» Google-Maps
Novartis Investigative Site
74101 Novy Jicin
CzechiaRekrutierend» Google-Maps
Novartis Investigative Site
100 34 Praha 10
CzechiaRekrutierend» Google-Maps
Novartis Investigative Site
140 59 Praha 4
CzechiaRekrutierend» Google-Maps
Novartis Investigative Site
DK 9000 Aalborg
DenmarkRekrutierend» Google-Maps
Novartis Investigative Site
DK-2100 Copenhagen
DenmarkRekrutierend» Google-Maps
Novartis Investigative Site
DK 5000 Odense C
DenmarkRekrutierend» Google-Maps
Novartis Investigative Site
00029 Helsinki
FinlandRekrutierend» Google-Maps
Novartis Investigative Site
FIN-33521 Tampere
FinlandRekrutierend» Google-Maps
Novartis Investigative Site
25030 Besancon Cedex
FranceRekrutierend» Google-Maps
Novartis Investigative Site
63011 Clermont Ferrand
FranceRekrutierend» Google-Maps
Novartis Investigative Site
85925 La Roche sur Yon Cedex
FranceRekrutierend» Google-Maps
Novartis Investigative Site
13273 Marseille
FranceRekrutierend» Google-Maps
Novartis Investigative Site
34298 Montpellier
FranceRekrutierend» Google-Maps
Novartis Investigative Site
59300 Valenciennes
FranceRekrutierend» Google-Maps
Novartis Investigative Site
94800 Villejuif
FranceRekrutierend» Google-Maps
Novartis Investigative Site
54645 Thessaloniki
GreeceRekrutierend» Google-Maps
Novartis Investigative Site
GR 115 22 Athens
GreeceRekrutierend» Google-Maps
Novartis Investigative Site
H 1122 Budapest
HungaryRekrutierend» Google-Maps
Novartis Investigative Site
D04 T6F Dublin 4
IrelandRekrutierend» Google-Maps
Novartis Investigative Site
85 796 Bydgoszcz
PolandRekrutierend» Google-Maps
Novartis Investigative Site
3000-075 Coimbra
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
1099 023 Lisboa
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
1400-038 Lisboa
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
1500 650 Lisboa
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
1649-019 Lisboa
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
4200-072 Porto
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
407280 Floresti
RomaniaRekrutierend» Google-Maps
Novartis Investigative Site
200347 Craiova
RomaniaRekrutierend» Google-Maps
Novartis Investigative Site
905900 Constanta
RomaniaRekrutierend» Google-Maps
Novartis Investigative Site
300425 Timisoara
RomaniaRekrutierend» Google-Maps
Novartis Investigative Site
83310 Bratislava
SlovakiaRekrutierend» Google-Maps
Novartis Investigative Site
812 50 Bratislava
SlovakiaRekrutierend» Google-Maps
Novartis Investigative Site
28223 Pozuelo de Alarcon
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This is a Phase III, randomized, double-blind, placebo-controlled, international,

multi-center trial. Approximately 234 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.

Participants randomized to the alpelisib-matching placebo plus fulvestrant arm who have

disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover to

be treated with alpelisib plus fulvestrant.

Unblinding a single participant at a site will be permitted after disease progression

confirmed by BIRC after discussion with the Novartis team to determine eligibility for

cross-over to treatment with alpelisib plus fulvestrant.

Ein-/Ausschlusskriterien

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.

- If female, then the participant must be in postmenopausal status. Postmenopausal

status is defined either by: prior bilateral oophorectomy, age ≥60 or age <60 and

amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen,

toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and

estradiol in the postmenopausal range per local normal range.

- 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).

- Participant must show the presence of a PIK3CA mutation(s) determined in tumor tissue

prior ro 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.

Exclusion Criteria:

- Participant with symptomatic visceral disease 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 (SERDs), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target

of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor

Other Inclusion and Exclusion Criteria do apply

Studien-Rationale

Primary outcome:

1. Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria (Time Frame - From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.):
To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to treatment with placebo plus fulvestrant. PFS is the defined as the time from randomization to date of randomization to the date of the first documented progression as per BIRC criteria using RECIST v1.1 or death due to any cause, whichever comes first.



Secondary outcome:

1. Overall survival (OS) (Time Frame - From the date of randomization to the date of death up to a maximum duration of 60 months):
To determine whether treatment with alpelisib plus fulvestrant prolongs overall survival (OS) compared to treatment with placebo plus fulvestrant. OS is defined as the time from randomization to the date of death due to any cause

2. Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria (Time Frame - From the date of randomization up to a maximum duration of 60 months):
To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. 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

3. Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria (Time Frame - From the date of randomization up to a maximum duration of 60 months):
To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. 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

4. Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria (Time Frame - From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months):
To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. 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.

5. Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria (Time Frame - From the date of randomization to the first documented response up to a maximum duration of 60 months):
To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. 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

6. PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status (Time Frame - From the date of randomization up to a maximum duration of 60 months):
To evaluate the association between PIK3CA mutation status with PFS upon treatment with alpelisib. PFS is the defined as the time from randomization to date of randomization to the date of the first documented progression as per BIRC criteria using RECIST v1.1 or death due to any cause, whichever comes first. Results will be presented by PIK3CA mutation status measured in circulating tumor deoxyribonucleic acid (ctDNA) collected at baseline.

7. Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline (Time Frame - From the date of randomization up to maximum duration of 60 months):
To evaluate treatment with alpelisib plus fulvestrant compared to placebo plus fulvestrant, with respect to time to deterioration of ECOG performance status. Time to definitive deterioration in ECOG PS is defined as the time from the date of randomization to the date when ECOG PS has definitively deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to the baseline category or above.

8. 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) (Time Frame - From the date of randomization up to maximum duration of 60 months):
To evaluate patient-reported outcomes of alpelisib plus fulvestrant compared to placebo and fulvestrant. Time from date of randomization to date of event, defined as at least a 10% worsening from baseline with no later improvement above this threshold observed during the course of the treatment or until death due to any cause, in the global health status/QOL and symptom scale scores of EORTC QLQ-C30, a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items and is composed of both multi-item scales and single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items and a global health status/QoL scale. The scales and single-item measures range in score from 0 - 100. A high scale score represents a higher response level.

9. Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30 (Time Frame - From the date of randomization up to maximum duration of 60 months):
To evaluate patient-reported outcomes of alpelisib plus fulvestrant compared to placebo and fulvestrant. Change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment. EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items and is composed of both multi-item scales and single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items and a global health status/QoL scale. The scales and single-item measures range in score from 0 - 100. A high scale score represents a higher response level.

10. Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2) (Time Frame - From the date of randomization up to maximum duration of 60 months):
To explore the long-term benefit intermediate to PFS and OS. PFS2 is defined as time from date of randomization to the first documented progression on nextline therapy or death from any cause, whichever occurs first. Disease progression will be determined based on investigator assessment of progression on next-line therapy.

Studien-Arme

  • Experimental: 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.
  • Placebo Comparator: 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. Participants who have disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover to be treated with alpelisib plus fulvestrant

Geprüfte Regime

  • Alpelisib:
    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:
    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:
    Alpelisib-matching placebo (tablets) administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

Quelle: ClinicalTrials.gov


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"Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor."

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