Targeting ATR in Soft-tissue Sarcomas
Targeting ATR in Soft-tissue Sarcomas: a Randomized Phase II Study. TARSARC Study
Institut Bergonié
72 participants
Feb 9, 2022
INTERVENTIONAL
Conditions
Summary
Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of berzosertib in association with gemcitabine
Eligibility
Inclusion Criteria18
- Histologically confirmed leiomyosarcomas.
- Metastatic or unresectable locally advanced disease,
- Documented progression according to RECIST v1.1 confirmed by central review,
- Age ≥ 18 years,
- ECOG ≤ 1,
- 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.
Exclusion Criteria24
- 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.
Interventions
Gemcitabine will be administered by intravenous 30-minutes infusion on days 1 and 8 every 3 weeks, at a fixed dose of 1000 mg/m². Berzosertib will be administered intravenously on days 2 and 9 every 3 weeks (210 mg/m²). A treatment cycle consists of 3 weeks (i.e., 21 days) and will be administered during hospitalization.
Gemcitabine will be administered by intravenous 30-minutes infusion on days 1 and 8 every 3 weeks, at a fixed dose of 1000 mg/m². A treatment cycle consists of 3 weeks (i.e., 21 days) and will be administered during hospitalization.
Locations(6)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04807816