2024-519624-24-00尚未招募2 期
"H3RAKLES": Tucatinib and trastuzumab in HER3-mutant and HER2-not amplified metastatic breast cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 9
- 主要终点
- Clinical benefit rate (CBR), defined as the proportion of patients who achieved a complete response (CR), a partial response (PR), or had stable disease (SD) for 24 weeks or more, according to the investigator-assessed RECIST v1.1 criteria.
研究概览
简要总结
To demonstrate that ERBB3 mutations are actionable in breast cancer in terms of 24 weeks clinical benefit rate
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
- 是
入选标准
- •Molecular screening step: availability of a formalin-fixed paraffin-embedded (FFPE) block with >10% tumor tissue (it is recommended to provide the most recently collected tumor sample).
- •Having received ≥ 2 previous chemotherapy lines for advanced breast cancer
- •Class IV or V somatic ERBB3 mutation as determined on a tumor sample obtained during the molecular screening step
- •ECOG performance status ≤ 2
- •Evaluable disease, per RECIST v1.1 inclusion criteria
- •Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment
- •Adequate organ function: a.Creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines; b.Total bilirubin ≤1.5 X upper limit of normal (ULN), except for patients with known Gilbert’s disease, who may enroll if the conjugated bilirubin is ≤1.5 X ULN; c.Transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 2.5 X ULN (≤ 5 X ULN if the patient has liver metastases)
- •Women of childbearing potential (WCBP) must have a negative serum pregnancy test < 7 days prior to first dose of treatment. A woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as the absence of menses for 12 months without an alternative cause.
- •WCBP (as defined above) and men with partners of childbearing potential must agree to use a highly effective birth control method during the study and for 3 months after completion of investigational treatment.
- •Patients should be eligible for the treatment step according to the investigator’s opinion.
- •Patients must be covered by a health insurance plan.
- •Molecular screening step: the tumor sample must have been obtained less than 5 years before inclusion
- •Patients able to provide signed informed consent.
- •Molecular screening step: prior signature of a written informed molecular screening consent.
- •Molecular screening step: patients should be eligible for the treatment step according to the investigator’s opinion.
- •Molecular screening step: patients must be covered by a health insurance plan.
- •Molecular screening step: patients able to provide signed informed consent.
- •Age ≥ 18 years
- •Metastatic or unresectable breast cancer
- •HER2-negative (defined as having an IHC 0+, IHC 1+, or IHC 2+ and ISH non-amplified, per ASCO/CAP guidelines) on last assessable tumor sample
排除标准
- •Having received any prior treatment targeting HER
- •Prior treatment with trastuzumab deruxtecan is allowed, per label, in patients with HER2-low metastatic breast cancer (IHC 1+ or 2+, ISH non-amplified)
- •Leptomeningeal metastases
- •Major surgery (including surgery of brain metastases) < 21 days prior to first dose of treatment
- •Evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment
- •Have known myocardial infarction or unstable angina within 24 weeks prior to first dose of study treatment
- •Have clinically significant cardiopulmonary disease such as: • Ventricular arrhythmia requiring therapy, • Uncontrolled hypertension (defined as persistent systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mm Hg on antihy) due to complications of advanced malignancy, • Hypoxia requiring supplementary oxygen therapy except when oxygen therapy is needed only for obstructive sleep apnea, • Presence of ≥ Grade 2 QTc prolongation on screening ECG, • Conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes: o Congenital or acquired long QT syndrome, o Family history of sudden death, o History of previous drug-induced QT prolongation, o Current use of medications with known and accepted associated risk of QT prolongation
- •Are known carriers of active Hepatitis B or Hepatitis C or have other known chronic liver disease
- •Are known to be positive for human immunodeficiency virus (HIV)
- •Altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent.
- •Patients who have difficulty undergoing trial procedures for geographic, social or psychological reasons
- •Person deprived of liberty or under guardianship
- •History of allergic reactions to trastuzumab or tucatinib or chemically similar drugs
- •Patients who are pregnant, breastfeeding, or planning a pregnancy from time of informed consent until 7 months after the final dose of study drug
- •Inability to swallow pills or having a significant gastro-intestinal disease or a history of surgery which would preclude the adequate oral absorption of medications
- •Having used a strong CYP2C8 inhibitor within a duration of 5 half-lives prior to the first dose of study treatment, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment (see Appendix B and Appendix C)
- •Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-central nervous system (CNS) radiation, or experimental agent ≤ 3 weeks prior to the first dose of study treatment, except gonadotropin releasing hormone (GnRH) agonists
- •Participation in another interventional clinical trial.
- •Symptomatic and untreated brain metastases or brain metastases requiring urgent treatment, or brain metastases requiring a dose > 2 mg of dexamethasone (or equivalent)
- •Whole brain radiotherapy < 21 days prior to first dose of treatment, stereotactic radiotherapy < 7 days prior to first dose of treatment
结局指标
主要结局
Clinical benefit rate (CBR), defined as the proportion of patients who achieved a complete response (CR), a partial response (PR), or had stable disease (SD) for 24 weeks or more, according to the investigator-assessed RECIST v1.1 criteria.
Clinical benefit rate (CBR), defined as the proportion of patients who achieved a complete response (CR), a partial response (PR), or had stable disease (SD) for 24 weeks or more, according to the investigator-assessed RECIST v1.1 criteria.
次要结局
- Progression-free survival (PFS), defined as the time from inclusion to progression or death; Objective response rate, defined as the proportion of patients who achieved a CR or PR according to the investigator-assessed RECIST v1.1 criteria; and duration of response, defined as the time between the first observation of a PR or a CR, and progressive disease or death
- Adverse Events (AEs) and Serious Adverse Events (SAEs), per CTCAE v5.0, considered by the investigator as related to trastuzumab or tucatinib.
- QLQ-C30 QoL questionnaire with the QLQ-BR42 module will be filled at inclusion, at cycles 1 and 3 and at the end of the treatment.
- Exploratory: relationship between biomarkers (including, but not limited to, DNA, RNA and proteins analyses) in blood, plasma, and/or tumor and either (1) presence of an ERBB3 mutation and (2) treatment efficacy.
研究者
François-Clement BIDARD
Scientific
Institut Curie
研究点 (9)
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