NCT04807816招募中2 期
Targeting ATR in Soft-tissue Sarcomas: a Randomized Phase II Study. TARSARC Study
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
- 72
- 试验地点
- 11
- 主要终点
- Assessment of the antitumor activity of berzosertib combined with gemcitabine
研究概览
简要总结
Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of berzosertib in association with gemcitabine
详细描述
This is a multicenter, prospective, open-labeled, 2-arm, non-comparative randomized (2:1) phase II trial. Patients will be randomized between arm A (gemcitabine + berzosertib) and arm B (gemcitabine) with two patients randomized in arm A for one patient randomized in arm B.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 confirmed leiomyosarcomas.
- •Metastatic or unresectable locally advanced disease,
- •Documented progression according to RECIST v1.1 confirmed by central review,
- •Age ≥ 18 years,
- •Life expectancy > 3 months,
- •No more than 3 previous line of systemic therapy for advanced disease,
- •Patients must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
- •Patients must have measurable disease defined as per RECIST v1.1
- •Patient must comply with the collection of tumor biopsies, and tumors must be accessible for biopsy,
- •At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
- •Adequate hematological, renal, metabolic and hepatic function
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
- •Both women of childbearing potential and men must agree to use a highly effective method of contraception 28 days before start of first dose of study drug
- •No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
- •Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment
- •Voluntarily signed and dated written informed consent prior to any study specific procedure,
- •Patients with a social security in compliance with the French law.
排除标准
- •Previous treatment with Gemcitabine, or berzosertib or other ATR inhibitor,
- •Evidence of progressive or symptomatic central nervous system or leptomeningeal metastases,
- •Women who are pregnant or breast feeding,
- •Participation to a study involving a medical or therapeutic intervention in the last 30 days,
- •Previous enrolment in the present study,
- •Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
- •Known hypersensitivity to any involved study drug or any of its formulation components,
- •Has known active hepatitis B or hepatitis C,
- •Has a known history of Human Immunodeficiency Virus or known acquired immunodeficiency syndrome
- •Any of the following cardiac or cardiovascular criteria :
- •Congestive heart failure ≥ New York Heart Association (NHYA) class 1,
- •Unstable angina , new-onset angina
- •Myocardial infarction less than 6 months before start of study drug
- •Uncontrolled cardiac arrhythmias,
- •Participants with Li Fraumeni syndrome and/or ataxia telangiectasia,
- •Active autoimmune disease:
- •Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible,
- •Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at dose ≤ 10 mg or 10 mg equivalent prednisone day,
- •Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular or inhalation) are acceptable.
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident , deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication,
- •Patients with oral anticoagulation based on Vitamine K antagonist,
- •Treatment by potent inhibitors or inducers of CYP3A4
- •Vaccination with yellow fever or by any other live attenuated vaccine in the last 30 days,
- •Individuals deprived of liberty or placed under legual guardianship.
研究组 & 干预措施
Standard Arm B: treatment by gemcitabine alone
Other
Patients with advanced leiomyosarcomas will be treated with with gemcitabine alone (control arm)
干预措施: Gemcitabine (Drug)
Experimental Arm A: treatment by berzosertib combined with gemcitabine
Experimental
Patients with advanced leiomyosarcomas will be treated with berzosertib combined with gemcitabine
干预措施: Association of berzosertib with gemcitabine (Drug)
结局指标
主要结局
Assessment of the antitumor activity of berzosertib combined with gemcitabine
时间窗: 6 months
Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.
Assessment of the antitumor activity of gemcitabine
时间窗: 6 months
Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.
次要结局
- 6-month objective response rate (ORR) for patients treated by berzosertib in association with gemcitabine(6 months)
- 6-month objective response rate (ORR) for patients treated by gemcitabine alone(6 months)
- Best overall response for patients treated by berzosertib in association with gemcitabine(throughout the treatment period, an expected average of 6 months)
- Best overall response for patients treated by gemcitabine alone(throughout the treatment period, an expected average of 6 months)
- 1-year progression-free survival for patients treated by berzosertib in association with gemcitabine(1 year)
- 1-year progression-free survival for patients treated by gemcitabine alone(1 year)
- 2-year progression-free survival for patients treated by berzosertib in association with gemcitabine(2 years)
- 2-year progression-free survival for patients treated by gemcitabine alone(2 years)
- 1-year overall survival for patients treated by berzosertib in association with gemcitabine(1 year)
- 1-year overall survival for patients treated by gemcitabine alone(1 year)
- 2-year overall survival for patients treated by berzosertib in association with gemcitabine(2 years)
- 2-year overall survival for patients treated by gemcitabine alone(2 years)
- 6-month objective response according to CHOI criteria, independently for each arm(6 months)
- Best overall response according to CHOI criteria, independently for each arm(throughout the treatment period, an expected average of 6 months)
- Safety profile independently for each arm: Common Terminology Criteria for Adverse Event version 5(throughout the treatment period, an expected average of 6 months)
- Tumor immune cells levels(before treatment onset and cycle 2 day 1 (each cycle is 21 days))
- Blood cytokines levels(baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days))
- Blood lymphocytes levels(baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days))
- Blood kynurenine levels(baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days))
研究者
研究点 (11)
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