NCT04879121招募中2 期
A Phase II Basket Study of the Oral TRK Inhibitor Larotrectinib (BAY2757556) in Subjects With NTRK Amplification Positive and Pan-TRK Positive Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Overall response
研究概览
简要总结
This phase II trial studies the effect of larotrectinib in treating patients with NTRK gene amplification positive solid tumors that have spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Larotrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE:
I. To determine overall response rate (ORR) to larotrectinib sulfate (larotrectinib) in patients with advanced solid tumors harboring NTRK amplification and pan-TRK expression by immunohistochemistry (IHC), calculated as the proportion of subjects with confirmed complete (CR) or partial response (PR) as best response and as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and Response Assessment in Neuro-Oncology (RANO) criteria in primary central nervous system (CNS) tumor.
SECONDARY OBJECTIVES:
I. To evaluate the duration of response (DOR) in subjects with CR or PR as best response.
II. To estimate the proportion of subjects with any tumor regression as best response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 16 years of age
- •Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene amplification identified through molecular assays (such as IHC and any next-generation sequencing [NGS] platform, reference lab NGS, or in house NGS platform) as routinely performed at The University of Texas MD Anderson Cancer Center or other similarly-certified laboratories. The minimum level of amplification is 7 copies. This rationale of amplification level is based on data from MOCLIA at The University of Texas MD Anderson Cancer Center
- •Must have received prior standard therapy appropriate for tumor type and stage of disease, or, in the opinion of the investigator, is unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy
- •Must have at least one measurable lesion as defined by RECIST v1.
- •Subjects with primary CNS tumors should meet the following criteria:
- •Must have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to cycle 1 day 1 (C1D1) of therapy, as recommended or appropriate for the tumor type
- •Must have >= 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO), with the size of at least one of the measurable lesions >= 1 cm in each dimension
- •Must have imaging study within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least five days immediately before and during the imaging study
- •Eastern Cooperative Oncology Group (ECOG) score =<
- •If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky performance score (KPS) >= 70 %
- •Archived tumor tissue. If archival tissue is unavailable, an on-study tumor biopsy should be attempted if it can be safely performed
- •Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) or < 5 x ULN if liver function abnormalities are due to underlying malignancy
- •Total bilirubin < 2.5 x ULN, except in cases of biliary obstruction. Subjects with a known history of Gilberts disease and an isolated elevation of indirect bilirubin are eligible
- •Serum creatinine < 2.0 x ULN or estimated glomerular filtration rate >= 30 mL/minute using the Cockcroft-Gault formula
- •Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
- •Willingness of men and women of reproductive potential to use two effective birth control methods, one used by the subject and another by his/her partner, for the duration of treatment and for 3 months following study completion
排除标准
- •Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib or five half-lives, whichever is shorter, and without clinically significant toxicities from that therapy
- •Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK. However, subjects who received less than 28 days of such treatment and discontinued because of intolerance or toxicity are eligible
- •Symptomatic or unstable brain metastases that needs corticosteroid usage. Subjects with asymptomatic brain metastases or primary CNS tumors are eligible
- •Uncontrolled concurrent malignancy that would limit assessment of efficacy. Allowed diseases may include, but are not limited to in situ cancers of cervix, breast, or skin, superficial bladder cancer, limited-stage prostate cancer, and basal or squamous cancers of the skin
- •Active uncontrolled systemic bacterial, viral, or fungal infection, unstable cardiovascular disease or other systemic disease that would limit compliance with study procedures. Unstable cardiovascular disease is defined as:
- •Persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy
- •Myocardial infarction within 3 months of screening
- •Stroke within 3 months of screening
- •Inability to discontinue treatment with a strong cytochrome P450 (CYP450), 3A4 (CYP3A4) inhibitor or inducer prior to start of treatment
- •Pregnancy or lactation
研究组 & 干预措施
Treatment (larotrectinib sulfate)
Experimental
Patients receive larotrectinib sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of unacceptable toxicity. Patients who experience disease progression and are deriving clinical benefit from larotrectinib may continue treatment per physician discretion.
干预措施: Larotrectinib Sulfate (Drug)
结局指标
主要结局
Overall response
时间窗: Up to 2 years post-treatment
Will be scored by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
次要结局
- Incidence of adverse events(Up to 4 weeks (after the final dose of the last cycle of treatment (between 21 and 35 days))
- Best overall response of confirmed complete response or partial response(Up to 2 years post-treatment)
- Growth modulation index(Up to 2 years post-treatment)
- Overall survival(From initiation of treatment to death from any cause, assessed up to 2 years)
- Duration of response(From the date complete response or partial response is first noted (whichever response is recorded first), to the date that recurrence or progressive disease is first documented or to date of death, assessed up to 2 years)
- Progression-free survival(From initiation of larotrectinib to disease progression or death due to any cause, whichever occurs first, assessed up to 2 years)
- Clinical benefit rate(Up to 2 years post-treatment)
- Change in clinical safety laboratory values and vital signs(Baseline up to 2 years post-treatment)
研究者
研究点 (1)
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