진행성 ER+ 유방암에서 LEE011, BYL719 및 Letrozole 연구
진행성 ER+ 유방암 성인 환자에서 LEE011 및 BYL719와 Letrozole의 조합에 대한 Ib/II상 다기관 연구
The purpose of this trial is to inform the future clinical development of the two investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha inhibitor).
This is a multi-center, open-label Phase Ib study. The Phase Ib dose escalation will estimate the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole (Arms 3 and 4).
The Phase Ib dose escalation part will be followed by Phase Ib dose expansions to further characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the combinations. Optional crossover for patients who have progressed while on dose escalation or dose expansion with doublet treatment on Arms 1 or 2 to be treated with the triplet combination (Arm 3) after the determination of the RP2D for Arm 3; is no longer permitted after protocol amendment 6.
Approximately 270 adult women with ER+/HER2- locally advanced or metastatic breast cancer will be enrolled.
연구 개요
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
확장된 액세스
연락처 및 위치
연구 장소
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Seoul, 대한민국, 03080
- Novartis Investigative Site
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California
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San Diego, California, 미국, 92103
- Univ of California at San Diego Moores Cancer Ctr
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San Francisco, California, 미국, 94143
- UCSF Medical Center
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Florida
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Tampa, Florida, 미국, 33612
- H Lee Moffitt Cancer Center and Research Institute
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Massachusetts
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital SC-5
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Tennessee
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Nashville, Tennessee, 미국, 37203
- Tennessee Oncology
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Nashville, Tennessee, 미국, 37232
- Vanderbilt University Medical Ctr
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Texas
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Amarillo, Texas, 미국, 79124
- Texas Oncology
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San Antonio, Texas, 미국, 78229
- Mays Cancer Ctr Uthsa Mdacc
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Washington
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Tacoma, Washington, 미국, 98405
- Northwest Medical Specialties
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Bellinzona, 스위스, 6500
- Novartis Investigative Site
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Madrid, 스페인, 28050
- Novartis Investigative Site
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Madrid, 스페인, 28009
- Novartis Investigative Site
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Seville, 스페인, 41013
- Novartis Investigative Site
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Valencia, 스페인, 46010
- Novartis Investigative Site
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Glasgow, 영국, G12 0YN
- Novartis Investigative Site
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Manchester, 영국, M20 2BX
- Novartis Investigative Site
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PI
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Pisa, PI, 이탈리아, 56126
- Novartis Investigative Site
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Marseille, 프랑스, 13273
- Novartis Investigative Site
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Paris, 프랑스, 75475
- Novartis Investigative Site
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Saint-Herblain, 프랑스, 44805
- Novartis Investigative Site
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New South Wales
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Westmead, New South Wales, 호주, 2145
- Novartis Investigative Site
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Victoria
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Parkville, Victoria, 호주, 3050
- Novartis Investigative Site
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Western Australia
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Nedlands, Western Australia, 호주, 6009
- Novartis Investigative Site
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Postmenopausal, Estrogen-receptor positive and/or Progesterone-receptor positive breast cancer
- Phase Ib dose escalation only: Any number of prior lines of endocrine therapy is allowed with the exception of cytotoxic therapy which is limited to one prior line administered in the advanced (metastatic or locally advanced) setting.
- Phase Ib dose expansions Arms 1, 2 and 3
- No prior systemic treatment in the advanced (metastatic or locally advanced) setting with the exception of treatment with letrozole for a maximum of one month prior to starting study treatment.
- Patients who received (neo)adjuvant therapy for breast cancer are eligible. Prior therapy with letrozole or anastrozole in the (neo)adjuvant setting is permitted if the disease-free interval is greater than 12 months from the completion of treatment.
Exclusion Criteria:
- HER2-overexpression in the patient's tumor tissue
- Patients with active CNS or other brain metastases
- Major surgery within 2 weeks
- Acute or chronic pancreatitis
- Bilateral diffuse lymphangitic carcinomatosis
- Another malignancy within 3 years
- Receiving hormone replacement therapy that cannot be discontinued
- Impaired cardiac function
- Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or with fasting glucose ≥ 126 mg/dL / 7.0 mmol/L or hemoglobin A1c >6.5%), history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus.
- Other protocol-defined inclusion/exclusion criteria may apply
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: LEE011 + letrozole Arm 1
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day |
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4. Letrozole 2.5 mg/day |
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실험적: BYL719 + letrozole Arm 2
BYL719 - daily (dose escalating) letrozole - 2.5 mg/day |
Letrozole 2.5 mg/day BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4 |
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실험적: LEE011 + BYL719 + letrozole Arm 3
LEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day |
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4. Letrozole 2.5 mg/day BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4 |
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실험적: LEE011+ BYL719+letrozole Arm 4
LEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day |
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4. Letrozole 2.5 mg/day BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4 |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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용량 제한 독성(DLT)의 발생률 - 1b상에만 해당
기간: 28일
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28일
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Safety and tolerability
기간: Average 18 months
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Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity. |
Average 18 months
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PK profiles of LEE011 and letrozole
기간: 18 months
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To characterize PK profiles of LEE011 and Letrozole. |
18 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Safety and tolerability of LEE011 in combination with letrozole, BYL719 in combination with letrozole, and the triple combination of LEE011 +BYL719 with letrozole
기간: Average 24 months
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Safety and tolerability will be determined by type, frequency and severity of adverse events and laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 |
Average 24 months
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Plasma concentration-time profiles of LEE011, BYL719 and letrozole
기간: Average 24 months
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To characterize the PK profiles of LEE011, BYL719, and letrozole when used in combination as well as to evaluate any other clinically significant metabolites that may be identified. |
Average 24 months
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Overall Response Rate (ORR)
기간: Average 24 months
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ORR is defined as the proportion of patients with a best overall response of complete response or partial response. |
Average 24 months
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Duration of Response (DOR)
기간: Average 24 months
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DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. |
Average 24 months
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Progression Free Survival (PFS)
기간: Average 24 months
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PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. |
Average 24 months
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Pharmacokinetics (PK) parameters, including but not limited to AUCtau, Cmin, Cmax, Tmax, accumulation ratio (Racc)
기간: Average 24 months
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To characterize the PK profiles of LEE011, BYL719, and letrozole when used in combination as well as to evaluate any other clinically significant metabolites that may be identified. |
Average 24 months
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Safety and tolerability of the triple combination of LEE011 +BYL719 with letrozole in patients previously treated with either doublet
기간: Average 24 months
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Safety and tolerability will be determined by type, frequency and severity of adverse events and laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 |
Average 24 months
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공동 작업자 및 조사자
수사관
- 연구 책임자: Novartis Pharmaceuticals, Novartis Pharmaceuticals
간행물 및 유용한 링크
일반 간행물
- Ji Y, Yartsev V, Quinlan M, Serra P, Wang Y, Chakraborty A, Miller M. Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials. Clin Pharmacokinet. 2023 Mar;62(3):493-504. doi: 10.1007/s40262-022-01206-2. Epub 2023 Feb 17.
- Ji Y, Wang C, Combes FP, Ho YY, Fasching PA, Untch M, Zarate JP, Crown J. Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer. Clin Pharmacokinet. 2026 Aug;65(8):1217-1228. doi: 10.1007/s40262-026-01643-3. Epub 2026 Jun 23.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정된)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- CLEE011X2107
- 2023-509511-84-00 (레지스트리 식별자: EU CT Number)
- 2023 (미국 NIH 보조금/계약)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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