2022-502667-38-00招募中2 期
(20289) A Phase 2 Basket Study of the Oral TRK Inhibitor larotrectinib in Subjects with NTRK Fusion-Positive Tumors
Bayer Consumer Care AG, Bayer AG13 个研究点 分布在 6 个国家目标入组 41 人开始时间: 2024年1月19日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 41
- 试验地点
- 13
- 主要终点
- Best overall response of confirmed complete response (CR) or partial response (PR) as determined by an independent radiology review committee using RECIST v1.1 or RANO criteria, as appropriate to tumor type.
研究概览
简要总结
To determine the overall response rate (ORR) as determined by an independent radiology review committee and measured by the proportion of subjects with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) criteria, as appropriate, following treatment with larotrectinib in subjects with an advanced cancer harboring a fusion involving NTRK1, NTRK2, or NTRK3 (collective referred to as NTRK fusions).
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Overall
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly-certified laboratories. Subjects who have an NTRK gene fusion identified in a lab where CLIA or equivalent certification cannot be confirmed by the Sponsor at the time of consent may have been enrolled in Cohort 9 as per protocol versions 1.0 - 8.
- •From protocol version 9.0: CLIA or similar certification of the lab performing the fusion assay is required. However, patients may be included after discussion with the sponsor if the lab performing the fusion assay is not CLIA or similar certified.
- •Capable of giving signed informed consent as described in protocol which includes compliance with the requirements, restrictions listed in the informed consent form (ICF), and in this protocol.
- •" For subjects eligible for enrollment to bone health cohort only: life expectancy of at least 6 months, based on investigator assessment."
- •Subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
- •"Subjects must have at least one measurable lesion as defined by RECIST v1.1 (Eisenhauer et al. 2009). Subjects with solid tumors without RECIST v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to Cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type. Subjects with primary central nervous system (CNS) tumors should meet the following criteria: a. Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type. b. Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice. c. Imaging study performed within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study. d. Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment. For subjects eligible for enrollment to bone health cohort, inclusion criterion 3 is modified as the following: e. Subjects must have at least one lesion at baseline (measurable or non-measurable as defined by RECIST v1.1 or RANO criteria, as appropriate to tumor type). f. Subjects with primary CNS tumors must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment."
- •At least 18 years of age
- •Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤
- •If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) ≥ 50%.
- •Tumor tissue before treatment (mandatory). If neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor.
- •"Adequate organ function as defined by the following criteria: a. Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN), or AST and ALT < 5 x ULN if liver function abnormalities are due to underlying malignancy b. Total bilirubin < 2.5 x ULN, except in the setting of biliary obstruction. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible c. Serum creatinine < 2.0 x ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockcroft-Gault formula: (140- age) x body weight (kg) x 0.85 (if female)/serum creatinine (mg/dL) x 72 with either result acceptable for enrollment."
- •Ability to comply (or for guardian to ensure compliance) 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 double effective birth control methods, defined as one used by the subject and another by his/her partner, for the duration of treatment and for 1 month following study completion.
排除标准
- •Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib or 5 half-lives, whichever is shorter, and without recovery of acute and/or clinically significant toxicities from that therapy.
- •Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
- •Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (TRK). Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.
- •Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.) Subjects with primary CNS tumors are eligible.
- •Uncontrolled concurrent malignancy that would limit assessment of efficacy of larotrectinib. Allowed conditions 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 Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures. Unstable cardiovascular disease is defined as: a. In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy. b. Myocardial infarction within 3 months of screening. c. Stroke within 3 months of screening."
- •Inability to discontinue treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer
- •Currently recovering from AEs/ ADRs due to previous treatments (excluding alopecia). Inclusion is only advised once the AE/ADR resolves or recovers to baseline or at least to CTCAE grade
- •Known or suspected hypersensitivity against the active substance or any of the ingredients of the Investigational Medicinal Product (IMP).
- •Known history of Human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations.
结局指标
主要结局
Best overall response of confirmed complete response (CR) or partial response (PR) as determined by an independent radiology review committee using RECIST v1.1 or RANO criteria, as appropriate to tumor type.
Best overall response of confirmed complete response (CR) or partial response (PR) as determined by an independent radiology review committee using RECIST v1.1 or RANO criteria, as appropriate to tumor type.
次要结局
- Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST v1.1 or RANO criteria, as appropriate to tumor type
- Duration of response (DOR): determined for subjects with best overall response of confirmed CR or PR by 1) an independent radiology review committee and 2) the treating Investigator
- Clinical benefit rate (CBR): best overall response of confirmed CR, PR, or stable disease lasting 16 or more weeks following the initiation of Larotrectinib
- Rate of subjects that have any tumor regression as a best response, measured as shrinkage of target lesions
- Progression-free survival (PFS)
- Overall survival (OS)
- Comparison of PFS following initiation of Larotrectinib to that following the line of therapy immediately preceding Larotrectinib in each subject who has received prior therapy
- Number of subjects with AEs categorized by severity. (including all, serious, and those considered treatment related.)
- Changes from baseline in clinical safety laboratory values and vital signs
- The concordance of prior molecular profiling that detected NTRK fusion within the subject’s tumor with the diagnostic test being evaluated by the sponsor
研究者
Therapeutic Area Head
Scientific
Bayer AG
研究点 (13)
Loading locations...
相似试验
进行中（未招募）
1 期
A study to learn how well the drug larotrectinib works in adults withdifferent solid cancers with a change in the genes called NTRK fusioSolid tumors harboring NTRK fusionMedDRA version: 21.1Level: LLTClassification code: 10065147Term: Malignant solid tumor Class: 10029104MedDRA version: 23.0Level: PTClassification code: 10081769Term: NTRK gene fusion overexpression Class: 100000004850CTIS2022-502667-38-00Bayer Consumer Care AG210
招募中
2 期
A phase II trial investigating Gemcitabine/Oxaliplatin/Rituximab with Tafasitamab (MOR208) for patients aggressive Lymphoma.2024-514775-17-00Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR64
进行中（未招募）
2 期
A MULTICENTER, SINGLE-ARM, THREE COHORT, PHASE II TRIAL OF PATRITUMAB DERUXTECAN (HER3-DXD) IN PATIENTS WITH ACTIVE BRAIN METASTASES FROM HER3-EXPRESSING ADVANCED BREAST CANCER AND NON–SMALL CELL LUNG CANCER, AND IN PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS FROM HER3-EXPRESSING ADVANCED SOLID TUMORS (The TUXEDO-3 Study)2023-503251-10-00Medica Scientia Innovation Research S.L.60
进行中（未招募）
1 期
A study to test the safety and efficacy of the drug larotrectinib for the treatment of tumors with NTRK-fusion in childreSolid tumors harboring NTRK fusionMedDRA version: 21.0Level: LLTClassification code: 10007959Term: Central nervous system neoplasm NOS Class: 10029104MedDRA version: 21.1Level: LLTClassification code: 10065147Term: Malignant solid tumor Class: 10029104MedDRA version: 20.1Level: HLTClassification code: 10007960Term: Central nervous system neoplasms malignant NEC Class: 10029205MedDRA version: 21.0Level: PTClassification code: 10007958Term: Central nervous system neoplasm Class: 100000004864MedDRA version: 23.0Level: PTClassification code: 10081769Term: NTRK gene fusion overexpression Class: 100000004850CTIS2022-502668-20-00Bayer Consumer Care AG155
已完成
不适用
Comparison Of Clinical And Radiological Success Of Pulpotomy Treatments Performed With Proroot MTA, NeoPUTTY MTA, TheraCal PT In Primary TeethNCT07260357Necmettin Erbakan University90