Fulvestrant (F)+Placebo vs F+Palbociclib First Line for Postmenopausal Hormone Receptor+ Advanced Breast Cancer (FLIPPER)
2020년 2월 3일 업데이트: Spanish Breast Cancer Research Group
Phase II Study to Compare Fulvestrant (F) 500mg Plus Placebo vs F 500mg Plus Palbociclib as First Line Treatment for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer Sensitive to Endocrine Therapy. GEICAM/2014-12
This is an international, multicentre, double-blind, controlled, randomized phase II study comparing the efficacy and safety of fulvestrant in combination with palbociclib versus fulvestrant plus placebo in postmenopausal women with HR-positive/HER2-negative metastatic breast cancer who have received ≥5 years of endocrine therapy in the adjuvant setting as treatment for early disease and remained disease free for > 12 months following its completion or have "de novo" metastatic disease.
연구 개요
상세 설명
Patients must have at least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI or plan x-ray. Patients with bone-only disease must have a lytic or mixed (lytic + blastic) lesion, which has not been previously irradiated and can be accurately assessed by CT/MRI or x-ray. Approximately 190 patients will be randomized 1:1 between the experimental arm (approximately 95 patients treated with fulvestrant plus palbociclib) and the control arm (approximately 95 patients treated with fulvestrant plus placebo).
Primary Objective:
• To compare the efficacy of fulvestrant in combination with palbociclib versus fulvestrant plus placebo in terms of the rate of Progression-Free Survival (PFS) at 1 year in postmenopausal women with HR-positive/HER2-negative metastatic breast cancer previously treated with endocrine therapy for at least 5 years and remaining disease free for more than 12 months following its completion or have "de novo" metastatic disease
연구 유형
중재적
등록 (실제)
189
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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A Coruña, 스페인, 15009
- Centro Oncologico de Galicia
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Barcelona, 스페인, 08003
- Hospital Del Mar
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Barcelona, 스페인, 08916
- Hospital Universitario Germans Trias i Pujol
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Barcelona, 스페인, 08026
- Hospital de la Santa Creu y Sant Pau
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Córdoba, 스페인, 14004
- Hospital Universitario Reina Sofia
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Jaen, 스페인, 23007
- Complejo Hospitalario de Jaén
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Leon, 스페인, 24080
- Complejo Asistencial Universitario de León
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Madrid, 스페인, 28034
- Hospital Universitario Ramon y Cajal
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Madrid, 스페인, 28040
- Hospital Clinico Universitario San Carlos
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Madrid, 스페인, 28492
- Hospital Universitario de Fuenlabrada
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Málaga, 스페인, 29011
- Hospital Regional Universitario de Málaga
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Sevilla, 스페인, 41013
- Hospital Universitario Virgen del Rocío
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Sevilla, 스페인, 41009
- Hospital Universitario Virgen De La Macarena
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Sevilla, 스페인, 41014
- Hospital Universitario de Valme
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Sevilla, 스페인, 41013
- Hospital Quirón Sagrado Corazón de Sevilla
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Valencia, 스페인, 46010
- Hospital Clínico Universitario de Valencia
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Valencia, 스페인, 46014
- Hospital General Universitario Valencia
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Valencia, 스페인, 46026
- Hospital Universitario i Politècnic La Fé
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Zaragoza, 스페인, 50009
- Hospital Universitario Miguel Servet
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Asturias
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Oviedo, Asturias, 스페인, 33011
- Hospital Universitario Central de Asturias
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Baleares
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Palma De Mallorca, Baleares, 스페인, 07198
- Hospital Son Llatzer
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Palma de Mallorca, Baleares, 스페인, 07120
- Hospital Universitari Son Espases
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Barcelona
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Terrassa, Barcelona, 스페인, 08221
- Hospital Universitario Mútua Terrassa
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Madrid
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Parla, Madrid, 스페인, 28981
- Hospital Universitario Infanta Cristina
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Pozuelo de Alarcón, Madrid, 스페인, 28223
- Hospital Universitario Quiron de Madrid
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Pontevedra
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Vigo, Pontevedra, 스페인, 36204
- Complejo Hospitalario Universitario Vigo
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Tarragona
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Reus, Tarragona, 스페인, 43204
- Hospital Universitario Sant Joan Reus
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Cork, 아일랜드
- Bon Secours Hospital
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Dublin, 아일랜드
- Beaumont Hospital
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Dublin, 아일랜드
- Mater Misericordiae University Hospital
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Galway, 아일랜드
- Galway University Hospital
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Waterford, 아일랜드
- University Hospital Waterford
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
여성
설명
Inclusion Criteria:
- The patient has signed and dated the informed consent document and it has been obtained before conducting any procedure specifically for the study.
- Availability of a tumor tissue sample, archival (primary tumour) or from the metastatic lesions (preferable) for the central ER, PgR and HER2 testing.
- Histological/cytological confirmation of breast cancer with evidence of metastatic disease (loco-regional or distant), not amenable to resection or radiation therapy with curative intent.
- Documented positive hormone receptor status (> or = 1% of tumour cells with oestrogen receptor [ER] and/or progesterone receptor [PgR] expression) based on central testing on the most recent tumour biopsy.
- Documented HER2-negative tumour based on central testing on the most recent tumour biopsy. HER2-negative tumour is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio <2 or for single probe assessment a HER2 copy number <4.
- Patients must have received at least 5 years of endocrine therapy in the adjuvant setting as treatment for early disease and remained disease free for more than 12 months following its completion or have "de novo" metastatic disease. Patients that have been scheduled 5 years with adjuvant endocrine therapy and stopped treatment, by patient's own decision, after completing at least 3 years of treatment, can be also be included as long as they have remained free of disease 3 years after discontinuing the endocrine therapy.
- Patients must have at least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, plan x-ray or physical examination. Clinical lesions will only be considered measurable when they are superficial and ≥10mm diameter as assessed using callipers (e.g. skin nodules). Patients with bone-only disease must have a lytic or mixed (lytic + blastic) lesion, which has not been previously irradiated and can be accurately assessed by CT/MRI according to RECIST version 1.1.
Postmenopausal patient, defined as a woman fulfilling any one of the following criteria (based on the NCCN definition of menopause [National Comprehensive Cancer Network 2008]):
- Prior bilateral oophorectomy.
- Age > 60 years.
- Age ≤ 60 years and with amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle stimulating hormone and estradiol in the postmenopausal range.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
- At least 18 years of age.
- Life expectancy ≥ 12 weeks.
Adequate organ and bone marrow function:
- ANC ≥ 1,500/mm3 (1.5x109/L);
- Platelets ≥ 100,000/mm3 (100x109/L);
- Haemoglobin (Hgb) ≥ 9g/dL (90g/L);
- Serum creatinine ≤ 1.5xUpper Limit of Normal (ULN) or estimated creatinine clearance ≥ 60ml/min as calculated using the method standard for the institution;
- Total serum bilirubin ≤ 1.5xULN (<3xULN if Gilbert´s disease);
- AST and/or ALT ≤ 3xULN (≤5xULN if liver metastases present);
- Alkaline Phosphatase (AP) ≤ 2.5xULN (≤5xULN if bone or liver metastases present).
- Patients consent to biological sample provision for biomarker exploratory analysis.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria:
- Prior systemic therapy for metastatic disease. Note: patients with a local recurrent disease treated with surgery (R0) and receiving a "second hormonal adjuvant therapy for five years" will be allowed, provided they have remained disease free for more than 12 months following its completion.
- Have "de novo" locally advanced disease.
- Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval.
- Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitis spread, or any known bone marrow infiltration due to breast cancer. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not significantly compromised as a result of disease.
- Treatment with a non-approved or experimental drug within 4 weeks before randomization.
- Prior treatment with any CDK4/6 inhibitor or fulvestrant.
- Current or prior malignancy within previous 5 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix).
History of:
- Bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or long-term (>6 months) anticoagulant therapy (other than antiplatelet therapy and low dose coumarin derivatives provided that the International Normalised Ratio (INR) is less than 1.6). Hypersensitivity to active or inactive excipients of fulvestrant, palbociclib/placebo or castor oil.
- Any severe concomitant condition which makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the trial protocol, e.g. uncontrolled cardiac disease or uncontrolled diabetes mellitus.
- QTc interval > 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
- Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (eg, hypocalcaemia, hypokalaemia, hypomagnesaemia).
- Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastro-paresis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhoea of CTCAE grade > 1.
- Prior hematopoietic stem cell or bone marrow transplantation.
- Known human immunodeficiency virus infection.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: PD-0332991(Palbociclib)+fulvestrant(FaslodexTM)
Fulvestrant 500mg, on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) in combination with Palbociclib, 125 mg, orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles.
|
Palbociclib, 125 mg, orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles. Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first
다른 이름들:
Fulvestrant 500mg, two 5ml intramuscular injections (one in each buttock), on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first
다른 이름들:
|
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활성 비교기: Placebo+fulvestrant(FaslodexTM)
Fulvestrant 500mg on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) in combination with Placebo orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles.
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Fulvestrant 500mg, two 5ml intramuscular injections (one in each buttock), on days 1, 15 (±3 days) of Cycle 1, and then on Day 1 of each subsequent 28 day cycle (±3 days) Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first
다른 이름들:
Placebo orally once daily from day 1 to day 21 followed by 7 days off treatment on every 28 days cycles. Patients will continue to receive their assigned treatment until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs firs |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Efficacy in terms of the rate of Progression-Free Survival (PFS)
기간: at 1 year
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assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by the investigator
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at 1 year
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Progression-Free Survival (PFS)
기간: an average of 40-44 months since FPFV (approximately Ago2019)
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the time from the date of randomization to the first documented progressive disease, using RECIST version 1.1, or death from any cause, whichever occurs first
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an average of 40-44 months since FPFV (approximately Ago2019)
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Objective Response Rate (ORR)
기간: at 1 year and to be updated with further analyses
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the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline.
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at 1 year and to be updated with further analyses
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Clinical Benefit Rate (CBR)
기간: at 1 year and to be updated with further analyses
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Complete Response (CR) plus Partial Response (PR) plus stable disease (SD) lasting ≥ 24 weeks (+/- 2 weeks) according to RECIST version 1.1.
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at 1 year and to be updated with further analyses
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Overall Survival (OS).
기간: an average of 40-44 months since FPFV(approximately Ago2019). A formal analysis will be performed when at least 60% of patients have died (2021)
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the time from the date of randomization to the date of death from any cause.
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an average of 40-44 months since FPFV(approximately Ago2019). A formal analysis will be performed when at least 60% of patients have died (2021)
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1 year and 2 year survival probabilities
기간: 1 year and 2 year
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the percentage of patients without death from any cause out of the randomised patients (calculated using the Kaplan-Meier technique).
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1 year and 2 year
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Incidence of adverse events occurring during the study, and their relatedness to the study drug/medications (safety and tolerability).
기간: at 1 year and to be updated with further analyses
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Safety will be assessed by standard clinical and laboratory tests.
Adverse events will be graded according to NCI-CTCAE version 4.0
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at 1 year and to be updated with further analyses
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Patient reported outcomes of health-related quality of life based on EORTC QLQ-C30 Global Health Status/Quality of Life and Physical Function
기간: at 1 year and to be updated with further analyses
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Generic aspects of quality of life will be assessed.
Changes (mean score) from baseline and time to deterioration will be analyzed.Health Status/QoL and Physical Function and EORTC QLQ-BR23 Breast Module from baseline
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at 1 year and to be updated with further analyses
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Patient reported outcomes of health-related quality of life based on EORTC QLQ-BR23 Breast Module.
기간: at 1 year and to be updated with further analyses
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Disease-specific treatment measurements will be assessed.
Changes (mean score) from baseline and time to deterioration will be analyzed.
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at 1 year and to be updated with further analyses
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Biomarker analyses
기간: Up to 5 years
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Identify promising biomarkers of response to fulvestrant plus palbociclib and fulvestrant plus placebo.
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Up to 5 years
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
수사관
- 연구 책임자: Study Director, Hospital Del Mar
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2016년 2월 17일
기본 완료 (실제)
2020년 1월 11일
연구 완료 (예상)
2023년 12월 1일
연구 등록 날짜
최초 제출
2016년 1월 5일
QC 기준을 충족하는 최초 제출
2016년 2월 18일
처음 게시됨 (추정)
2016년 2월 24일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2020년 2월 5일
QC 기준을 충족하는 마지막 업데이트 제출
2020년 2월 3일
마지막으로 확인됨
2020년 2월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- GEICAM/2014-12
- 2015-002437-21 (EudraCT 번호)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .