A Phase II Study of the Safety, Tolerability and Antitumor Activity of Tucatinib in Combination With Eribulin and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer

Criterium, Inc.12 个研究点分布在 1 个国家目标入组 30 人2024年1月30日

概览

简要总结

The purpose of this study is to evaluate the safety and efficacy of the three-drug combination of tucatinib, trastuzumab, and eribulin in patients with de novo and recurrent unresectable metastatic HER-2/neu positive breast cancer as assessed by ORR, PFS and OS after prior treatment with a taxane, trastuzumab, and T-DM1.

详细描述

In view of the potency of tucatinib for the treatment of brain metastases and its modest toxicity, it is important to evaluate the combination of this drug with other established anti-HER2 therapies. There remains a need to evaluate the efficacy of tucatinib with additional active agents in this area. Given the demonstrated activity of eribulin in metastatic breast cancer in general and in her2 positive disease combined with trastuzumab in particular, this study proposes to evaluate the safety and efficacy of the three-drug combination of eribulin, trastuzumab, and tucatinib. It is also important to ascertain the activity of this combination in patients who have previously received tucatinib, as little is known about whether resistance to tucatinib plus one chemotherapy drug confers resistance to tucatinib with a different partner drug.

注册库

clinicaltrials.gov

开始日期

2024年1月30日

结束日期

2027年8月1日

最后更新

3个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Criterium, Inc.

责任方

Sponsor

入排标准

入选标准

•Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC)
•Have received previous treatment with trastuzumab deruxtecan in the metastatic setting or have recurred within 6 months of receiving this treatment in the adjuvant or neoadjuvant setting. Prior taxane, capecitabine and T-DM1 are not required. Prior tucatinib therapy is allowed. Patients for whom Trastuzumab is contraindicated are not permitted. Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by site investigator),or be intolerant of last systemic therapy.
•Have measurable or non-measurable disease assessable by RECIST 1.1
•Be at least 18 years of age at time of consent.
•Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0,1 or 2
•Have a life expectancy of at least 6 months, in the opinion of the site investigator.
•Have adequate hepatic function as defined by the following:
•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
•Transaminases \[aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT)\] ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)
•Have adequate baseline hematologic parameters as defined by:

排除标准

•Have previously been treated with eribulin for metastatic disease (except in cases where eribulin was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity)
•History of exposure to the following cumulative doses of anthracyclines:
•Doxorubicin \> 360 mg/m2
•Epirubicin \> 720 mg/m2
•Mitoxantrone \> 120 mg/m2
•Idarubicin \> 90 mg/m2
•Liposomal doxorubicin (e.g. Doxil, Caelyx, Myocet) \> 550 mg/m2
•History of allergic reactions to trastuzumab, eribulin, 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 one of the excipients in the study drugs
•Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent ≤ 3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial. An exception for the washout of hormonal therapies is gonadotropin releasing hormone (GnRH) agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications.
•Have any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:

研究组 & 干预措施

Tucatinib/Eribulin/Trastuzumab

* The initial dose of trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV), unless trastuzumab was administered within the prior 4 weeks, then the initial dose of trastuzumab will be administered at a dose of 6 mg/kg. Each trastuzumab dose is given once every 21 days, except in specific circumstances where it may be given weekly to compensate for modifications in treatment schedule * Tucatinib 300 mg orally twice daily (PO BID) every day (Days 1-21) of each 21-day cycle using a modified schedule of events. Subcutaneous trastuzumab is given only once every three weeks as there is no allowance for weekly dosing. * Eribulin will be given at a dose of 1.1 mg/M2 intravenously over a 2-5 minute period on days 1 and 8 of each 21-day cycle.

干预措施: Tucatinib

Tucatinib/Eribulin/Trastuzumab

* The initial dose of trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV), unless trastuzumab was administered within the prior 4 weeks, then the initial dose of trastuzumab will be administered at a dose of 6 mg/kg. Each trastuzumab dose is given once every 21 days, except in specific circumstances where it may be given weekly to compensate for modifications in treatment schedule * Tucatinib 300 mg orally twice daily (PO BID) every day (Days 1-21) of each 21-day cycle using a modified schedule of events. Subcutaneous trastuzumab is given only once every three weeks as there is no allowance for weekly dosing. * Eribulin will be given at a dose of 1.1 mg/M2 intravenously over a 2-5 minute period on days 1 and 8 of each 21-day cycle.

干预措施: Eribulin

Tucatinib/Eribulin/Trastuzumab

* The initial dose of trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV), unless trastuzumab was administered within the prior 4 weeks, then the initial dose of trastuzumab will be administered at a dose of 6 mg/kg. Each trastuzumab dose is given once every 21 days, except in specific circumstances where it may be given weekly to compensate for modifications in treatment schedule * Tucatinib 300 mg orally twice daily (PO BID) every day (Days 1-21) of each 21-day cycle using a modified schedule of events. Subcutaneous trastuzumab is given only once every three weeks as there is no allowance for weekly dosing. * Eribulin will be given at a dose of 1.1 mg/M2 intravenously over a 2-5 minute period on days 1 and 8 of each 21-day cycle.

干预措施: Trastuzumab

结局指标

主要结局

Evaluate the relative toxicity/tolerability of these therapeutic agents when used in combination in this patient cohort

时间窗: 2 years

Rate of grade 3 -4 toxicity, incidence of dose limiting toxicities, incidence of dose holding, dose reductions, and discontinuations of any and/or all of the three treatment agents

To assess the safety and tolerability of tucatinib in combination with eribulin and trastuzumab in patients with unresectable or recurrent metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, and trastuzumab deruxtecan.

时间窗: 2 years

Incidence of adverse events and serious adverse events. Rate of grade 3 -4 toxicity, incidence of dose limiting toxicities, incidence of dose holding, dose reductions, and discontinuations of any and/or all of the three treatment agents. Incidence of cardiac and pulmonary complications.