Phase II, Exploratory, Multicenter, Non Randomized, Single Agent Cohort Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 16
- 主要终点
- Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
研究概览
简要总结
This multicenter, non-randomized, Phase II study will assess the efficacy, safety, and pharmacokinetics of trastuzumab emtansine in participants with HER2 overexpressing locally advanced (unresectable and not treatable with curative intent) or metastatic urothelial bladder cancer (UBC), locally advanced (unresectable and not treatable with curative intent) or metastatic pancreatic cancer/cholangiocarcinoma with advanced disease where cure is no longer possible and where no other treatment options are available anymore. Participants will receive intravenous (IV) infusion of trastuzumab emtansine as Regimen A (2.4 milligrams per kilogram [mg/kg], weekly [qw]) or Regimen B (3.6 mg/kg, every 3 weeks [q3w]) until unacceptable toxicity, withdrawal of consent, disease progression (PD), or death, whichever occurs first. Based on tolerability and safety aspects, steering committee and Independent Data Monitoring Committee (iDMC) will decide on expansion of the study to include more participants with other carcinoma types.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ in greater than or equal to [>/=] 30 percent [%] of tumor cells): locally advanced (unresectable and not treatable with curative intent), or metastatic UBC or locally advanced (unresectable and not treatable with curative intent) or metastatic pancreatic cancer/cholangiocarcinoma
- •There must be no standard treatment options available for participants with the above HER2 overexpressing tumors and they must have undergone at least one prior platinum-based treatment for locally advanced (unresectable and not treatable with curative intent) or metastatic tumor (Note: for pancreatic cancer/cholangiocarcinoma, prior treatments are not required to be platinum-based.)
- •Participant's lesion should be measurable according to RECIST V1.1 on diagnostic computed tomography (CT) scan/magnetic resonance imaging (MRI); Target lesion(s) should not have been previously irradiated
- •At least one formalin-fixed paraffin-embedded (FFPE) biopsy of the primary tumor and/or from a metastatic site is required
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
- •No significant cardiac history and a current left ventricular ejection fraction (LVEF) >/=50%
- •Adequate organ function
- •Life expectancy of at least 12 weeks
排除标准
- •Participants with previous exposure to HER2-targeted therapies in any setting
- •Participants showing histologically confirmed focal HER2-expression, that is, less than (<) 30% of positively stained tumor cells
- •Participants with brain metastasis as the sole site of metastatic disease and/or are symptomatic or require therapy to control symptoms
- •Current uncontrolled hypertension (systolic greater than [>] 150 millimeters of mercury [mmHg] and/or diastolic >100 mmHg)
- •Current unstable angina pectoris
- •History of symptomatic congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria or ventricular arrhythmia that requires treatment
- •History of myocardial infarction within the last 6 months
- •Peripheral neuropathy, Grade >/=3
- •Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
- •Current severe, uncontrolled systemic disease
- •History of other malignancy within the last 5 years
- •Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C
- •Known prior severe hypersensitivity to trastuzumab and trastuzumab emtansine or the excipients of the investigational medicinal product (IMP)
- •Clinically significant bleeding within 30 days before enrollment
- •Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
- •Concurrent participation in any other therapeutic clinical trial
研究组 & 干预措施
Cohort 1 (UBC)
First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC will initially receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
干预措施: Trastuzumab Emtansine (Drug)
Cohort 2 (Pancreatic cancer/cholangiocarcinoma)
First six participants with metastatic pancreatic cancer/cholangiocarcinoma will receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).
干预措施: Trastuzumab Emtansine (Drug)
结局指标
主要结局
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
时间窗: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than \[\<\] 10 millimeter \[mm\]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.
次要结局
- Overall Survival (OS)(Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months))
- Progression-Free Survival (PFS)(Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months))
- Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)(Baseline up to approximately 18 months)
- Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria(Baseline up to approximately 18 months)
- Plasma/Serum Concentrations of Trastuzumab Emtansine(Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days)