Targeting ATR in Soft-tissue Sarcomas

NCT ID: NCT04807816

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-09
• Study Completion Date: 2027-12-31

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) with two patients randomized in arm A for one patient randomized in arm B.

Conditions

Leiomyosarcoma, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm A: treatment by berzosertib combined with gemcitabine

Patients with advanced leiomyosarcomas will be treated with berzosertib combined with gemcitabine

Group Type: EXPERIMENTAL

Association of berzosertib with gemcitabine

Intervention Type: DRUG

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.

Standard Arm B: treatment by gemcitabine alone

Patients with advanced leiomyosarcomas will be treated with with gemcitabine alone (control arm)

Group Type: OTHER

Gemcitabine

Intervention Type: DRUG

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.

Interventions

Association of berzosertib with gemcitabine

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.

Intervention Type: DRUG

Gemcitabine

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.

Intervention Type: DRUG

Other Intervention Names

Experimental; Control

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed leiomyosarcomas.

2. Metastatic or unresectable locally advanced disease,

3. Documented progression according to RECIST v1.1 confirmed by central review,

4. Age ≥ 18 years,

5. ECOG ≤ 1,

6. Life expectancy > 3 months,

7. No more than 3 previous line of systemic therapy for advanced disease,

8. 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,

9. Patients must have measurable disease defined as per RECIST v1.1

10. Patient must comply with the collection of tumor biopsies, and tumors must be accessible for biopsy,

11. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,

12. Adequate hematological, renal, metabolic and hepatic function

13. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.

14. 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

15. 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,

16. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment

17. Voluntarily signed and dated written informed consent prior to any study specific procedure,

18. Patients with a social security in compliance with the French law.

Exclusion Criteria

1. Previous treatment with Gemcitabine, or berzosertib or other ATR inhibitor,

2. Evidence of progressive or symptomatic central nervous system or leptomeningeal metastases,

3. Women who are pregnant or breast feeding,

4. Participation to a study involving a medical or therapeutic intervention in the last 30 days,

5. Previous enrolment in the present study,

6. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,

7. Known hypersensitivity to any involved study drug or any of its formulation components,

8. Has known active hepatitis B or hepatitis C,

9. Has a known history of Human Immunodeficiency Virus or known acquired immunodeficiency syndrome

10. 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,

11. Participants with Li Fraumeni syndrome and/or ataxia telangiectasia,

12. 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.

13. 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,

14. Patients with oral anticoagulation based on Vitamine K antagonist,

15. Treatment by potent inhibitors or inducers of CYP3A4

16. Vaccination with yellow fever or by any other live attenuated vaccine in the last 30 days,

17. Individuals deprived of liberty or placed under legual guardianship.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: collaborator

Institut Bergonié

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Bergonié

Bordeaux, , France

Site Status: RECRUITING

Centre Leon Berard

Lyon, , France

Site Status: RECRUITING

CHU Poitiers

Poitiers, , France

Site Status: RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

Site Status: WITHDRAWN

IUCT Oncopôle

Toulouse, , France

Site Status: RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Antoine ITALIANO, MD, PhD

Role: CONTACT

a.italiano@bordeaux.unicancer.fr

(0)5.56.33.33.33 ext. +33

Simone MATHOULIN-PELISSIER, MD, PhD

Role: CONTACT

s.mathoulin@bordeaux.unicancer.fr

Facility Contacts

Antoine ITALIANO, MD, PhD

Role: primary

a.italiano@bordeaux.unicancer.fr

Armelle DUFRESNE, MD

Role: primary

armelle.dufresne@lyon.unicancer.fr

Nicolas ISAMBERT, MD, PhD

Role: primary

nicolas.isambert@chu-poitiers.fr

Thibaud VALENTIN, MD

Role: primary

valentin.thibaud@iuct-oncopole.fr

Benjamin VERRET, MD

Role: primary

benjamin.verret@gustaveroussy.fr

Other Identifiers

2018-003835-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IB 2018-04

Identifier Type: -

Identifier Source: org_study_id