PADA-1 : Randomized, open label, multicentric phase III trial to evaluate the safety and efficacy of palbociclib in combination with hormone therapy driven by circulating DNA ESR1 mutation monitoring in estrogen receptor-positive, HER2-negative metastatic breast cancer patients

Unicancer79 个研究点分布在 1 个国家目标入组 1,000 人2024年6月7日

概览

阶段: 3 期
干预措施: 未指定
疾病 / 适应症: 未指定
发起方: Unicancer
入组人数: 1000
试验地点: 79
主要终点: The Progression-Free Survival (PFS) will be measured from the time of randomization (following rising ESR1 mutation detection) to the time of tumor progression (as assessed by the investigator per RECIST v1.1 criteria (Eisenhauer 2009)) or death (whichever comes first) – in randomized patients. Efficacy analyses will be performed using the local radiologist’s/investigator’s tumor assessments as primary data source.
状态: 进行中（未招募）
最后更新: 去年

概览研究者入排标准结局指标研究点相似试验

概览

简要总结

Population STEP1 to 3 : To assess the global safety of the combination of palbociclib + endocrine therapy in the whole population of patients, throughout the study, including the potential sequential administration of fulvestrant plus palbociclib, with focus on hematological toxicities. Population STEP2 : To assess whether a change of the hormone therapy associated with palbociclib (namely, an early switch from aromatase inhibitor with palbociclib to fulvestrant with palbociclib following ctDNA detection) will benefit patients in which rising ESR1 mutations are detected during treatment with palbociclib and aromatase inhibitor.

注册库

euclinicaltrials.eu

开始日期

2024年6月7日

结束日期

待定

最后更新

去年

研究类型

Interventional clinical trial of medicinal product

性别

Female

研究者

发起方

Unicancer

责任方

Principal Investigator

主要研究者

Nourredine AIT RAHMOUNE

Scientific

Unicancer

入排标准

入选标准

•STEP1 : Women with proven loco-regionally recurrent or metastatic disease adenocarcinoma of the breast not amenable to curative therapy with disease considered potentially sensitive to aromatase inhibitor
•STEP 1 : Adequate organ and marrow function as defined : Hemoglobin ≥ 90 g/L; Absolute neutrophil count ≥ 1.5 G/L; Platelet count ≥ 100 G/L; Serum bilirubin ≤ 1.5 × ULN. This will not apply to patients with confirmed Gilbert’s syndrome; ALT and AST ≤ 3 × ULN; Alkaline phosphatase ≤ 2.5× ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min as determined by Cockcroft-Gault (using actual body weight) formula for females [creatinine clearance =Weight (kg) × (140 - Age) × 0.85 (mL/min)/ (72 × serum creatinine (mg/dL))
•STEP 1 : Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and any protocol-related procedures including screening evaluations;
•STEP 1 : Resolution of all acute toxic effects or prior anti-cancer therapy or surgical procedures to NCI-CTCAE version 4.03 grade 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion);
•STEP 1 : Written informed consent obtained prior to performing any protocol-related procedures including screening evaluations;
•STEP 1 : Patient affiliated to a social security system.
•STEP 2 : Patients included and treated within the PADA-1 protocol, who received a combination of aromatase inhibitor and palbociclib;
•STEP 2 : Detection of a rise in circulating ESR1 mutation as defined in the protocol;
•STEP 2 : Absence of concomitant RECIST 1.1 proven tumor progression;
•STEP 2 : Life expectancy > 3 months;

排除标准

•STEP 1 : Locally advanced breast cancer or loco-regional relapse amenable for any treatment with curative intent;
•STEP 1 : History of mal-absorption syndrome or other condition that would interfere with enteral absorption;
•STEP 1 : Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent (excluding inhaled steroids);
•STEP 1 : Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral oedema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable and off anticonvulsants and steroids for at least 4 weeks before treatment start;
•STEP 1 : Known hypersensitivity to letrozole, anastrozole, exemestane, fulvestrant, palbociclib or any of their excipients;
•STEP 1 : Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia);
•STEP 1 : Patients treated within the last 7 days prior to treatment start in the trial with drug that are known to be CYP3A4 inhibitors, drugs that are known to be CIP3A4 inducers, or with patients who underwent a grapefruit and grapefruit juice cure;
•STEP 1 : Patients already included in another therapeutic trial evaluating an investigational medicinal product or having received an investigational medicinal product within 3 months;
•STEP 1 : History of previous: Any stage II, III, IV cancer within 5 years preceding patient enrollment in the trial – however multiple breast cancers (controlateral/ipsilateral cancers/local relapses) are allowed pending all tumor masses were ER+; Any history of hematological malignancy.
•STEP 1 : Persons deprived of their freedom or under guardianship or incapable of giving consent;

结局指标

主要结局

The Progression-Free Survival (PFS) will be measured from the time of randomization (following rising ESR1 mutation detection) to the time of tumor progression (as assessed by the investigator per RECIST v1.1 criteria (Eisenhauer 2009)) or death (whichever comes first) – in randomized patients. Efficacy analyses will be performed using the local radiologist’s/investigator’s tumor assessments as primary data source.

The safety will be assessed by the collection of grade ≥3 adverse events, using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 – in all included patients. The co-primary analysis will focus on grade ≥3 hematological toxicities and their associations with baseline characteristics.

次要结局

Progression-Free Survival will be measured from the time of cross-over to the time of tumor progression (as assessed by the investigator per RECIST 1.1) or death (whichever comes first) – in all patients undergoing the crossover.
Progression-Free Survival will be measured from the time of inclusion to the time of tumor progression (as assessed by the investigator per RECIST 1.1) or death (whichever comes first) – in all included patients including those switched to fulvestrant.
Time to strategy failure will be measured from the time of randomization until palbociclib+endocrine therapy discontinuation or death (whichever comes first)– in all randomized patients.
Chemotherapy-free survival will be measured from the time of randomization until the date of chemotherapy initiation or death (whichever comes first)– in all randomized patients. Anticancer treatments received after the study treatment discontinuation will be described.
Description of all extra-hematological grade ≥3 toxicities and SAEs incidence rate in the overall population and each treatment step.
Overall Survival measured from the date of inclusion to that of the patient’s death – in all included patients.
Quality of life score obtained through self-administered QLQ-C30 questionnaire at baseline, at randomization, and every 2 cycles until disease progression (including patients who perform a late switch from arm A to B) or until two years after inclusion whatever the step if patient did not undergo disease progression or rising ctDNA before 2 years.
Translational end points : ctDNA detection at different time points.