Status:

RECRUITING

Targeting ATR in Soft-tissue Sarcomas

Lead Sponsor:

Institut Bergonié

Collaborating Sponsors:

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Conditions:

Leiomyosarcoma, Adult

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of berzosertib in association with gemcitabine

Detailed Description

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) ...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

February 9 2022

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 1 2027

Estimated Enrollment :

72 Patients enrolled

Trial Details

Trial ID

NCT04807816

Start Date

February 9 2022

End Date

December 1 2027

Last Update

October 2 2025

Active Locations (6)

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Page 1 of 2 (6 locations)

1

Institut Bergonié

Bordeaux, France, 33076

2

Centre Leon Berard

Lyon, France, 69008

3

CHU Poitiers

Poitiers, France, 86000

4

Institut de Cancérologie de l'Ouest

Saint-Herblain, France, 44805