EUCTR2019-005017-39-GB进行中（未招募）1 期
Randomized, double-blind, phase 3 study of tucatinib or placebo in combination with ado-trastuzumab emtansine (T-DM1) for subjects with unresectable locally-advanced or metastatic HER2+ breast cancer (HER2CLIMB-02)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Seagen Inc.
- 入组人数
- 460
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Histologically confirmed HER2+ metastatic breast carcinoma, as determined by sponsor-designated central laboratory testing on tumor tissue submitted prior to randomization, from archival tissue or a newly-obtained baseline biopsy of an accessible tumor lesion that has not been previously irradiated is required
- •2. History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination. Prior pertuzumab therapy is allowed, but not required.
- •3. Have progression of unresectable LA/M breast cancer after last systemic therapy, or be intolerant of last systemic therapy
- •4. Measureable or non-measurable disease assessable by RECIST v1.1
- •5. HR (estrogen receptor [ER]/ progesterone receptor [PR]) status must be known prior to randomization
- •6. Age =18 years at time of consent
- •7. ECOG performance status score of 0 or 1
- •8. Life expectancy =6 months, in the opinion of the investigator
- •9. Adequate hepatic function (refer to protocol)
- •10. Adequate baseline hematologic parameters (refer to protocol)
- •11. Estimated glomerular filtration rate (GFR) =50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable
- •12. International normalized ratio (INR) and partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) = 1.5 X ULN, unless on medication known to alter INR and PTT/aPTT.
- •13. Left ventricular ejection fraction (LVEF) =50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment
- •14. For subjects of childbearing potential the following stipulations apply:
- •a. Must have a negative serum or urine pregnancy test result within 7 days prior to the first dose of study treatment. A subject with a false positive result and documented verification that the subject is not pregnant is eligible for participation.
- •b. Must agree not to try to become pregnant during the study and for at least 7 months after the final dose of study drug administration
- •c. Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 7 months after the final dose of study drug administration
- •d. If sexually active in a way that could lead to pregnancy, must consistently use highly effective methods of birth control starting at the time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study drug administration.
- •Please refer to protocol for a list of highly effective methods of birth control.
- •15. For subjects who can father children, the following stipulations apply:
- •a. Must agree not to donate sperm starting at time of informed consent and continuing throughout the study period and for at least 7 months after the final study drug administration
- •b. If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use a barrier method of birth control starting at time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study drug administration
- •c. If sexually active with a person who is pregnant or breastfeeding, must consistently use a barrier method of birth control starting at time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study drug administration
- •16. The subject or the subject’s legally acceptable representative must provide
排除标准
- •1. Prior treatment with tucatinib, neratinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for =21 days and was discontinued for reasons other than disease progression or severe toxicity)
- •2. Prior treatment with T-DM1
- •3. History of allergic reactions to trastuzumab or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed, or known allergy to any of the excipients in the study drugs
- •4. Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, experimental agent or participation in another interventional clinical trial =3 weeks prior to first dose of study treatment. An exception for the washout of hormonal therapies is gonadotropin releasing hormone agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications.
- •5. Any toxicity related to prior cancer therapies that has not resolved to = Grade 1, with the following exceptions:
- •- Alopecia;
- •- Neuropathy, which must have resolved to = Grade 2;
- •- Congestive heart failure (CHF), which must have been = Grade 1 in severity at the time of occurrence, and must have resolved completely
- •6. Clinically significant cardiopulmonary disease such as:
- •- Ventricular arrhythmia requiring therapy
- •- Symptomatic hypertension or uncontrolled asymptomatic hypertension as determined by the investigator
- •- Any history of symptomatic CHF, left ventricular systolic dysfunction or decrease in ejection fraction
- •- Severe dyspnea at rest (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or above) due to complications of advanced malignancy or hypoxia requiring supplementary oxygen therapy
- •- = Grade 2 QTc prolongation on screening electrocardiogram (ECG)
- •7. Known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment
- •8. Known carrier of Hepatitis B or Hepatitis C or has other known chronic liver disease
- •9. Known to be positive for human immunodeficiency virus.
- •10. Subjects who are pregnant, breastfeeding, or planning to become pregnant from time of informed consent until 7 months following the last dose of study drug
- •11. Unable to swallow pills or has significant gastrointestinal disease which would preclude the adequate oral absorption of medications
- •12. Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment. CYP3A4 or CYP2C8 inducers and inhibitors are also prohibited as concomitant medications within two weeks of discontinuation of tucatinib treatment. Use of sensitive CYP3A substrates should be avoided two weeks before enrollment and during study treatment.
- •13. Unable to undergo contrast MRI of the brain
- •14. Other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
- •15. Evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment
- •16. CNS Exclusion – Based on screening brain MRI, subjects must not have any of the following:
- •a. Any untreated brain lesions >2.0 cm in size, unless approved by the medical monitor
- •b. Ongoing use of systemic
研究者
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