NCT05625087进行中（未招募）2 期
A ctDNA Screening Program in Patients With HR+, HER2- Metastatic Breast Cancer for Detection of High-risk Relapse Patients on Any CDK4/6 Inhibitor and a Randomised Phase II Study Comparing Alpelisib Combined With Fulvestrant to Ribociclib Combined With Fulvestrant, in Patients With Persistent Targetable PIK3CA Mutations
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- UNICANCER
- 入组人数
- 162
- 试验地点
- 44
- 主要终点
- Progression-Free Survival in the study groups
研究概览
简要总结
After an initial screening phase (SAFIR 03 - SCREENING) to identify patients with blood circulating mutated-PIK3CA tumours persistent, patients will be enrolled in the treatment phase of SAFIR 03 (SAFIR 03 - ARRIBA) that was designed as a randomised, open-label, multicentre, phase II study, for comparison of alpelisib to ribociclib in combination with fulvestrant (as the continuation of the CDK4/6 inhibitor-fulvestrant strategy) in terms of progression-free survival (PFS).
详细描述
INDICATION The population eligible to the screening phase is composed of all women or men with HR+, HER2- metastatic breast cancer who are eligible for first-line treatment with a cyclin-dependent kinases (CDK) 4/6 inhibitor combined with fulvestrant (and a luteinizing hormone realeasing hormone (LH-RH) analogue in men and premenopausal women) in the context of the standard healthcare management. The screening will identify patients with high risk of relapse on any CDK4/6 inhibitor thanks to ctDNA kinetic between baseline and 4 weeks of treatment. The purpose is to early adapt the therapeutic intervention for ctDNA no drop patient to prevent from relapse. This study will propose an intervention for PIK3CA mutated patients with alpelisib vs. ribociclib. Other therapeutic approaches might be proposed to patients with wild type PIK3CA through other protocols.
The randomised study phase will include patients with persistent mutations on exons 4, 9 or 20* of PIK3CA ctDNA after 4 weeks of treatment with any CDK4/6 inhibitor-fulvestrant in first-line setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have signed a written informed consent prior to any study-specific screening procedures (the consent form specifically for the screening phase must be signed).
- •Patient is ≥18 years of age.
- •Patient has an histologically or cytologically confirmed metastatic breast cancer.
- •Patient has a HER2- breast cancer (without HER2 overexpression according to the ASCO-CAP 2018 guidelines).
- •Patient has hormone receptor-positive (HR+) breast cancer, defined as having oestrogen receptor (ER) and/or progesterone receptor (PR) expression in ≥10% of tumour cells.
- •Patient had a metastatic relapse during or within 1 year after termination of the adjuvant endocrine therapy.
- •Patient has not yet been treated in the metastatic breast cancer setting.
- •Patient is eligible for a first-line treatment with a marketed CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) in combination with fulvestrant, according to its marketing authorisation.
- •Eastern Cooperative Oncology Group (ECOG) performance status is ≤
- •Patient has an adequate bone marrow and organ function.
- •Measurable or evaluable disease according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1).
- •Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
- •Patient must be affiliated to the national social security (or equivalent).
排除标准
- •Prior exposure to PIK3CA-AKT or CDK4/6 inhibitors.
- •Patient that has initiated the CDK4/6 inhibitor treatment.
- •Patient with spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for ≥30 days before initiating the study treatment).
- •Participant with an established diagnosis of diabetes mellitus type I or not controlled type II (based on FG and HbA1c).
- •Patient unable to swallow tablets.
- •Patient with known hypersensitivity to any of the study treatment excipients, in particular patients with allergies to soya or peanuts.
- •Patients with a history of malabsorption syndrome or other condition that may interfere with enteral absorption: including but not limited to active intestine inflammation (e.g., Crohn's disease or ulcerative colitis) requiring immunosuppressive therapy.
- •Patient with any condition/disease for which the investigator considers that participating in the study is inappropriate or that may jeopardize treatment and protocol compliance.
- •Patient deprived of liberty or under the authority of a tutor.
- •RANDOMISED PHASE ( SAFIR 03 -ARRIBA)
- •Inclusion Criteria:
- •Patient must have signed a written informed consent prior to any procedures for the randomised study phase (the consent form specifically for the randomised study phase must be signed).
- •Patient has a circulating PIK3CA level of exon 4, 9 or 20 mutant* of PIK3CA ctDNA determined by circulating tumour DNA (ctDNA) assay after 4 weeks of treatment with any CDK4/6 inhibitor combined with fulvestrant.
- •Patient must have discontinued CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) at least 7 days before randomisation.
- •ECOG performance status is ≤
- •Patient's life expectancy is deemed ≥3 months.
- •Patient has an adequate bone marrow and organ function as defined by the following laboratory values:
- •Absolute neutrophil count (ANC) ≥1500/mm³,
- •Platelet count ≥100,000/mm³,
- •Haemoglobin ≥9.0 g/dL,
- •International normalised ratio (INR) ≤1.5 (unless the participant is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug),
- •Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥50 mL/min,
- •Total bilirubin ≤2× ULN (<3 ULN with documented Gilbert's disease) or direct bilirubin ≤ 1.5 × ULN,
- •aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or <5.0 x ULN if patient has liver metastasis,
- •Fasting Serum amylase ≤ 2 × ULN,
- •Fasting Serum lipase ≤ ULN,
- •Fasting plasma glucose (FPG) ≤140 mg/dL (or ≤7.7 mmol/L) and glycosylated haemoglobin (HbA1c) ≤6.4%.
- •Participant must have the following laboratory values within normal limits or corrected to within normal limits with supplements before randomisation
- •Potassium
- •Magnesium
- •Total Calcium (corrected for serum albumin)
- •Patient with parameters of standard 12-lead ECG (defined as the mean of triplicate ECGs performed) as follows, before randomisation:
- •QTcF interval <450ms (using Fridericia's correction),
- •Resting heart rate between 50-90 bpm.
- •Women of childbearing potential must have a negative serum pregnancy test result within 14 days of enrolment in the randomised trial phase.
- •Men or Women of childbearing potential must agree to the use of effective contraceptive for the study duration and for at least 2 year after the last dose of study treatment for women, and at least 21 days for men.
- •Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
- •Also numbered exon 5, 10 and 21 according to recent classification: Ensembl Transcript ID: ENST00000263967.4, RefSeq: NM_006218.
- •Exclusion Criteria:
- •Patient is eligible to chemotherapy because of visceral crisis.
- •Pregnant or lactating women.
- •Patient has received more than 2 cycles of the ongoing CDK4/6 inhibitor treatment combined with fulvestrant before randomisation.
- •Patient has interrupted the ongoing CDK4/6 inhibitor treatment for more than 14 days before randomisation.
- •Patient has evidence of clinical or radiological disease progression before randomisation.
- •Patient has unresolved adverse events (grade ≥1), except alopecia and grade ≥2 unresolved adverse events related to fulvestrant or the LH-RH analogue which are acceptable to randomisation.
- •Patient is considered at high medical risk because of severe or uncontrolled systemic disease, including but not limited to diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, chronic pancreatitis, chronic active hepatitis, active untreated/uncontrolled fungal, bacterial, or viral infections, as well as known active viral infections with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- •Participant has currently documented pneumonitis/interstitial lung disease (the chest CT scan performed before start of study treatment for the purpose of tumour assessment should be reviewed to confirm that there are no relevant pulmonary complications present).
- •Participant has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
- •Participant with unresolved osteonecrosis of the jaw.
- •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:
- 另有 20 项未显示
研究组 & 干预措施
ALPELISIB ARM
Experimental
Oral alpelisib (300 mg daily, in 28-day cycle) and fulvestrant as per standard practice. Moreover, men and premenopausal women will receive an LH-RH analogue (goserelin, leuprorelin, or triptorelin) every 28 days ±3 days, as per standard practice
干预措施: Alpelisib (Drug)
RIBOCICLIB ARM
Active Comparator
Oral ribociclib (600 mg daily, 3 weeks on, then 1 week off treatment in 28-day cycles) and fulvestrant as per standard practice. Moreover, men and premenopausal women will receive an LH-RH analogue (goserelin, leuprorelin, or triptorelin) every 28 days ±3 days, as per standard practice.
干预措施: Ribociclib (Drug)
结局指标
主要结局
Progression-Free Survival in the study groups
时间窗: From randomization to disease progression or death, up to 5 years
The PFS is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
次要结局
- Overall Survival in the study groups(From randomization to death, up to 5 years)
- Safety in each study groups.(Throughout study completion, up to 5 years)
- Progression Free Survival (PFS) in non-randomised patients(From randomization to death, up to 5 years)
- Objective response Rate (ORR) in the study groups(5 years)
- Duration of response in the study groups(5 years)
- Clinical Benefit Rate in the study groups(5 years)
- Time to Response in the study groups(From randomization to death, up to 5 years)
- To validate that randomised patients with residual PIK3CA on ctDNA present a poor outcome compare to non-randomised patient(From the date of initiation of standard of care to death, up to 5 years)
- Overall Survival (OS) in non-randomised patients(From the date of initiation of standard of care to death of any cause, up to 5 years)
研究者
研究点 (44)
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