Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer

Официальное название

A Phase 3 Randomized, Double-Blind, Active-Controlled Study of Palazestrant With Ribociclib Versus Letrozole With Ribociclib for the First-Line Treatment of ER+, HER2- Advanced Breast Cancer (OPERA-02)

Обзор

This phase 3 clinical trial compares the efficacy and safety of palazestrant with ribociclib to letrozole and ribociclib in women and men who have not received prior systemic anti-cancer treatment for advanced breast cancer.

Подробное описание

This is an international, multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: investigational arm) with letrozole in combination with ribociclib + palazestrant-matching placebo (Arm B: control arm).

This trial is seeking adult participants with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for advanced disease. Approximately 1,000 participants will be randomized in a 1:1 ratio to one of the two study arms.

Вмешательства

• Препарат Palazestrant
  Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.
• Препарат Letrozole-matching placebo
  Participants will be treated with letrozole-matching placebo once daily on a 4-week (28 day) cycle
• Препарат Ribociclib
  Participants will be treated with ribociclib 600 mg once daily on Days 1-21 of a 4-week (28 day) cycle.
• Препарат Letrozole
  Participants will be treated with letrozole 2.5 mg once daily on a 4-week (28-day) cycle
• Препарат Palazestrant matching-placebo
  Participants will be treated with palazestrant-matching placebo once daily on a 4-week (28-day) cycle

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)]

Вторичные конечные точки (11)

• Overall Survival (OS) [Срок оценки: From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)]
• Progression Free Survival (PFS) [Срок оценки: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)]
• Overall response Rate (ORR) [Срок оценки: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)]
• Duration of Response (DOR) [Срок оценки: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)]
• Clinical Benefit Rate (CBR) [Срок оценки: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)]
• Overall response Rate (ORR) [Срок оценки: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)]
• Duration of Response (DOR) [Срок оценки: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)]
• Clinical Benefit Rate (CBR) [Срок оценки: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)]
• Safety and tolerability [Срок оценки: Up to 42 days after end of treatment (estimated as up to 3.5 years)]
• Pharmacokinetics (PK) of palazestrant and ribociclib [Срок оценки: Every 28 days (estimated as up to 3.5 years)]
• Health-related patient-reported outcomes (PROs) [Срок оценки: Every 28 days (estimated as up to 3.5 years)]

Критерии участия

Критерии включения

• Adult female or male participants.
• ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy.
• Evaluable disease (measurable disease per RECIST 1.1 or bone-only disease).
• De novo advanced breast cancer or with disease recurrence occurring after 12 months of completing adjuvant endocrine therapy (with or without CDK4/6 inhibitors)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, hepatic, and renal functions.
• Female participants can be pre-, peri- or postmenopausal.
• Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist.

Критерии исключения

• Disease recurrence during adjuvant endocrine therapy
• Currently receiving or previously received systemic anti-cancer therapy for ER+, HER2- advanced breast cancer.
• Previously received treatment with fulvestrant, elacestrant or an investigational endocrine therapy in any setting.
• History of allergic reactions to study treatment.
• Any contraindications to letrozole and ribociclib.
• Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 43 центра

• Clinical Trial Site — Hot Springs
• Clinical Trial Site — Beverly Hills
• Clinical Trial Site — La Jolla
• Clinical Trial Site — Los Alamitos
• Clinical Trial Site — San Francisco
• Clinical Trial Site — Santa Barbara
• Clinical Trial Site — Aurora
• Clinical Trial Site — Denver
• … и ещё 35 центров

Испания · 15 центров

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South Korea · 12 центров

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Италия · 11 центров

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Австралия · 8 центров

• Clinical Trial Site — Sydney
• Clinical Trial Site — Waratah
• Clinical Trial Site — South Brisbane
• Clinical Trial Site — Adelaide
• Clinical Trial Site — Clayton
• Clinical Trial Site — Geelong
• Clinical Trial Site — Heidelberg
• Clinical Trial Site — Nedlands

Франция · 8 центров

• Clinical Trial Site — Pierre-Bénite
• Clinical Trial Site — Brest
• Clinical Trial Site — Plérin
• Clinical Trial Site — Besançon
• Clinical Trial Site — Montpellier
• Clinical Trial Site — Toulouse
• Clinical Trial Site — Bobigny
• Clinical Trial Site — Villejuif

Малайзия · 8 центров

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Польша · 7 центров

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Румыния · 6 центров

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Тайвань · 6 центров

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Бельгия · 5 центров

• Clinical Trial Site — Brussels
• Clinical Trial Site — Woluwe-Saint-Lambert
• Clinical Trial Site — Kortrijk
• Clinical Trial Site — Liège
• Clinical Trial Site — Charleroi

Чехия · 5 центров

• Clinical Trial Site — Hořovice
• Clinical Trial Site — Liberec
• Clinical Trial Site — Olomouc
• Clinical Trial Site — Prague
• Clinical Trial Site — Zlín

Таиланд · 5 центров

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Великобритания · 5 центров

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Греция · 4 центра

• Clinical Trial Site — Pátrai
• Clinical Trial Site — Athens
• Clinical Trial Site — Athens
• Clinical Trial Site — Thessaloniki

Австрия · 3 центра

• Clinical Trial Site — Krems
• Clinical Trial Site — Salzburg
• Clinical Trial Site — Linz

Германия · 3 центра

• Clinical Trial Site — Frankfurt
• Clinical Trial Site — Düsseldorf
• Clinical Trial Site — Torgau

Гонконг · 3 центра

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Венгрия · 3 центра

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Нидерланды · 3 центра

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Португалия · 3 центра

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Канада · 1 центр

• Clinical Trial Site — Toronto

Идентификаторы

NCT: NCT07085767 · OP-1250-302 · OPERA-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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