2023-507306-13-00招募中2 期
A Multicenter, Open-Label, Single-Arm, Phase II Trial Exploring the Maintenance of Trastuzumab and Pertuzumab Following Trastuzumab Deruxtecan as Induction Treatment for HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer Patients (The DEMETHER Study)
Medica Scientia Innovation Research S.L.40 个研究点 分布在 4 个国家目标入组 132 人开始时间: 2024年5月17日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 132
- 试验地点
- 40
- 主要终点
- 1-year PFS rate, defined as the rate of patients with absence of disease progression or death from any cause at 1 year after the treatment initiation, as determined locally by the investigator using RECIST v.1.1.
研究概览
简要总结
To determine the progression free survival (PFS) rate at 1 year of induction treatment with T-DXd followed by PHESGO as maintenance therapy in patients with HER2-positive unresectable locally advanced or MBC who have received no prior chemotherapy and/or HER2-targeted therapy for advanced disease (all patients).
To analyze the overall survival (OS) rate at 3 years of induction treatment with T-DXd followed by PHESGO as maintenance therapy in all patients.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
- •No prior chemotherapy and/or HER2-targeted therapy for advanced disease (one prior line of endocrine therapy is allowed for MBC).
- •Patients may have received adjuvant or neoadjuvant chemotherapy and/or HER2-targeted therapy before study treatment initiation, with a DFI from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of at least 12 months.
- •Patients with adequate bone marrow and organ function: Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within 7 days before first study treatment dose): White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 9.0 g/dL.
- •Patients with adequate bone marrow and organ function: Hepatic: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times the upper limit of normal (x ULN) (≤ 3 x ULN in patients with known history of Gilbert’s disease); alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 × ULN in patients with liver and/or bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases).
- •Patients with adequate bone marrow and organ function: Renal: Creatinine clearance ≥ 50 mL/min as determined by Cockcroft Gault (using actual body weight).
- •Patients with adequate bone marrow and organ function: Coagulation: International normalized ratio or prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN.
- •Resolution of all acute toxic effects of prior anticancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
- •Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 7 months after the last dose of study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period.
- •Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 4 months after the last dose of T-DXd or 7 months after the last dose of PHESGO to prevent pregnancy. Male participants must not donate or bank sperm during this same period.
- •Patient must be accessible for treatment and follow-up.
- •Female or male patients ≥ 18 years of age at the time of signing ICF.
- •ECOG performance status of 0-
- •Minimum life expectancy of ≥ 12 weeks at screening.
- •Evidence of HER2-overexpressing tumor status as per 2018 American Association of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 guidelines and confirmed by MEDSIR’s designated central lab.
- •Patients must have known estrogen receptor (ER) and progesterone receptor (PgR) status locally determined prior to study entry.
- •Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to treatment with curative intent.
- •Evaluable disease according to RECIST v.1.
- •Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue sample at the time of the inclusion. If archival tissue is not available, a newly obtained baseline biopsy of an accessible tumor lesion is required prior to start of study treatment.
排除标准
- •Current participation in another therapeutic clinical trial, except other translational studies.
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: Poorly controlled hypertension (i.e., systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg).
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: Symptomatic pericarditis.
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: Left ventricular ejection fraction (LVEF) < 55% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO).
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia), which is symptomatic or requires treatment (NCI-CTCAE grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, asymptomatic sustained ventricular tachycardia, or higher-grade atrioventricular [AV]-block, such as second-degree AV-block Type 2 [Mobitz 2] or third-degree AV-block). Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers will be permitted to enroll.
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: QT Interval Corrected by Fridericia’s formula (QTcF) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead ECG.
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
- •Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within three months of the study enrolment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
- •Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- •Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.
- •Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drug.
- •Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- •Has active primary immunodeficiency, known human immunodeficiency virus (HIV) infection.
- •Other active uncontrolled infection at the time of enrollment.
- •Receipt of live or attenuated vaccine within 30 days prior to the first dose of study treatment.
- •A history of uncontrolled seizures, CNS disorders, or serious and/or unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs or interfering with subject safety.
- •Known substance abuse or any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, contraindicate patient participation.
- •Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.
- •Has previously been treated with T-DXd in the adjuvant or neoadjuvant setting.
- •Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Note: Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of study treatment.
- •Has a concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor’s Medical Monitor is required.
- •Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.
- •Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks prior to start of study treatment.
- •Major surgical procedure or significant traumatic injury within 14 days before the first dose of study treatment or anticipation of need for major surgery within the course of the study treatment.
- •Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following: Unstable angina pectoris, documented myocardial infarction, or symptomatic cardiac heart failure (CHF) (New York Heart Association [NYHA] Class II-IV) within six months prior to study entry.
结局指标
主要结局
1-year PFS rate, defined as the rate of patients with absence of disease progression or death from any cause at 1 year after the treatment initiation, as determined locally by the investigator using RECIST v.1.1.
1-year PFS rate, defined as the rate of patients with absence of disease progression or death from any cause at 1 year after the treatment initiation, as determined locally by the investigator using RECIST v.1.1.
3-year OS rate, defined as the rate of patients alive at 3 years after treatment initiation, as determined locally by the investigator.
3-year OS rate, defined as the rate of patients alive at 3 years after treatment initiation, as determined locally by the investigator.
次要结局
- PFS, defined as the period from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.
- OS, defined as the period from treatment initiation to death from any cause, as determined locally by the investigator.
- ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1.
- CBR, defined as the rate of patients with objective response (CR or PR), or stable disease for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1.
- TTR, defined as the period from treatment initiation to the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR, as determined locally by the investigator using RECIST v.1.1.
- DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.
- Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator using RECIST v.1.1.
- Safety endpoints: Changes from baseline in the EORTC QLQ-C30, the EORTC QLQ-BR45, and the EQ-5D-5L scales and symptoms scores.
- Safety endpoints: Safety and tolerability as per NCI-CTCAE v.5.0.
- Exploratory endpoints: Association of prognostic and/or predictive biomarkers in tumor tissue and/or liquid biopsy with PFS, OS, ORR, CBR, TTR, DoR, and maximum tumor reduction.
- Exploratory endpoints: Efficacy endpoints for all patients according to different clinicopathological characteristics and prior treatment for early breast cancer.
- Exploratory endpoints: Association of treatment efficacy outcomes in all patients with radiological imaging biomarkers.
研究者
Alicia García
Scientific
Medica Scientia Innovation Research S.L.
研究点 (40)
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