NCT03036228已完成1 期
MTH1, A Phase I, Study on Tumors Inhibition, First in Human, First in Class
Thomas Helleday Foundation3 个研究点 分布在 1 个国家目标入组 63 人开始时间: 2017年1月14日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 3
- 主要终点
- Safety and tolerability of Karonudib (TH1579) will be evaluated.
研究概览
简要总结
Primary Objective
• To determine the safety and tolerability of Karonudib (TH1579) in escalating doses for the treatment of patients with advanced solid malignant tumours.
Secondary Objective
- To define DLT and MTD.
- To determine a recommended phase 2 dose (RP2D) and schedule.
- To determine the pharmacokinetics of Karonudib.
- To determine preliminary signs of clinical efficacy of Karonudib.
- To determine overall survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Age at least 18 years (there is no upper age limit but patients must be judged to have a "biologic" age of 75 years or less).
- •Life expectancy of at least 12 weeks (as per investigators clinical assessment).
- •ECOG PFS 0 or
- •Patients must have measurable disease based on RECIST 1.1 criteria or evaluable metastatic disease unless otherwise specified in specific patient groups.
- •Patients with any 1 of the following histologically confirmed tumors and who qualifies for new therapy and relapsing to/after standard therapy or the patient has refused or does not tolerate standard therapy Cohort 19
- •Histologically or cytologically confirmed adenocarcinoma of prostate that is metastatic, hormone-refractory (confirmed by testing serum testosterone), and clinically progressive following at least one prior hormonal regimen. Prostate cancer patients must have measurable (patient with measurable bi-dimensional disease) or evaluable disease (defined as the presence of a non-measurable abnormality on CT or on physical examination coupled with an abnormal PSA value) or PSA relapse (Obtain sequence of rising values at a minimum of 1-week intervals, 1.0 ng/mL minimal value). Patients can only have received a taxane therapy in the pre-metastatic hormone refractory setting
- •High Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer that can be assessed radiological, clinically or biochemically.
- •Cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies, or for which no standard therapy is available. Patients must have measurable disease based on RECIST 1.1 criteria or evaluable metastatic disease.
- •Biopsy-proven carcinoma of the cervix that is either locally advanced or metastatic.
- •Recurrent or metastatic head and neck adenocarcinoma who are not candidates for curative surgery or refusing surgical treatment
- •Adequate bone marrow, hepatic and renal function defined as:
- •Haemoglobin ≥ 95 g/L (blood transfusion not less than 21 days prior to screening).
- •Absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L.
- •Total bilirubin < 1.5 x ULN (does not apply to patients with Gilberts Syndrome).
- •AST and ALT ≤ 1.5 x ULN (or ≤ 3 x ULN in the presence of liver metastases).
- •Serum creatinine not over ≤ ULN (if serum creatinine is between 1 and 1.5 x ULN, patients may be eligible provided that the calculated GFR is at least 50 ml/min using Cockcroft-Gault method).
- •Albumin greater than or equal to 23 g/L.
- •Subject must be able to take oral medication.
- •Negative pregnancy test according to CTFG guidance 2014 for females of child-producing potential.
- •Known HIV-infected patients with undetectable viral loads will be eligible for the study. HIV testing is mandatory
排除标准
- •Age less than 18 years.
- •Less than 4 weeks since stopping previous systemic cancer treatment or less than 5 half lifes of prior therapy, whichever is shorter.
- •Less than 3 weeks since stopping palliative radiotherapy.
- •Less than 3 weeks after minor surgery.
- •Less than 6 months since a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke or TIA.
- •Congestive heart failure NYHA class ≥ II.
- •History of arrhythmias or arrhythmias discovered during the screening period (apart from atrial fibrillation without ventricular tachycardia and premature extra beats).
- •Patients requiring anti-arrhythmic drugs.
- •QTc interval >450 ms at baseline.
- •Use of fentanyl (must be stopped at least 1 week prior to initiation of Karonudib).
- •Use of anti-oxidants vitamins and acetylcysteine (must be stopped within 48 hours of starting treatment with Karonudib).
- •Use of antidepressant medications which are substrate for CYP2D6 (must be stopped at least 3 weeks prior to starting treatment with Karonudib).
- •Any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of study results.
- •Leptomeningeal metastases (patient with previously treated brain metastases are eligible provided that there is no evidence of disease progression for a minimum of 8 weeks prior to inclusion - in these cases a CNS MR is required within the screening period).
- •Known acute or chronic infection with hepatitis B or C that is untreated.
- •Pregnant or breast-feeding women.
- •Patients with reproductive potential not implementing accepted and effective means of contraception.
- •Participation in any other clinical trial within the previous 4 weeks.
- •Unable to comply with study procedures.
研究组 & 干预措施
Dose escalation
Experimental
Karonudib is an oral inhibitor of MTH1 supplied as an oral solution and now as tablets. Each cycle is defined as 28 days.
干预措施: Karonudib (Drug)
结局指标
主要结局
Safety and tolerability of Karonudib (TH1579) will be evaluated.
时间窗: 28 days, first treatment cycle for the patient.
Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD). DLTs will be assessed during first cycle of therapy, week 1-4 based on Haematological toxicity and Non-haematological toxicity. MTD: The highest dose of Karonudib that does not cause unacceptable side effects is defined as the MTD.
次要结局
- To determine the pharmacokinetics of Karonudib.(28 days, first treatment cycle for the patient)
- To determine preliminary signs of clinical efficacy of Karonudib.(54 days, two treatment cycles for the patient)
研究者
研究点 (3)
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