Targeting ATR in Soft-tissue Sarcomas (TARSARC)

May 4, 2026 updated by: Institut Bergonié

Targeting ATR in Soft-tissue Sarcomas: a Randomized Phase II Study. TARSARC Study

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
58

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Lyon, France, 69008
        • Centre Léon Bérard
      • Poitiers, France, 86000
        • CHU Poitiers
      • Toulouse, France, 31059
        • IUCT Oncopole
      • Villejuif, France, 94805
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental Arm A: treatment by berzosertib combined with gemcitabine
Patients with advanced leiomyosarcomas will be treated with berzosertib combined with gemcitabine
Drug: 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.

Other Names:
  • Experimental
Other: Standard Arm B: treatment by gemcitabine alone
Patients with advanced leiomyosarcomas will be treated with with gemcitabine alone (control arm)
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.

Other Names:
  • Control

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Assessment of the antitumor activity of berzosertib combined with gemcitabine
Time Frame: 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.
6 months
Assessment of the antitumor activity of gemcitabine
Time Frame: 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.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
6-month objective response rate (ORR) for patients treated by berzosertib in association with gemcitabine
Time Frame: 6 months
Objective response is defined as complete response (CR) or partial response (PR) as per adapted RECIST v1.1.
6 months
6-month objective response rate (ORR) for patients treated by gemcitabine alone
Time Frame: 6 months
Objective response is defined as complete response (CR) or partial response (PR) as per adapted RECIST v1.1.
6 months
Best overall response for patients treated by berzosertib in association with gemcitabine
Time Frame: throughout the treatment period, an expected average of 6 months
Best overall response is defined as the best reponse across all time points (RECIST v1.1). The best overall response rate is determined once all the data for the patient is known
throughout the treatment period, an expected average of 6 months
Best overall response for patients treated by gemcitabine alone
Time Frame: throughout the treatment period, an expected average of 6 months
Best overall response is defined as the best reponse across all time points (RECIST v1.1). The best overall response rate is determined once all the data for the patient is known
throughout the treatment period, an expected average of 6 months
1-year progression-free survival for patients treated by berzosertib in association with gemcitabine
Time Frame: 1 year
Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST v1.1) or death (from any cause), whichever occurs first
1 year
1-year progression-free survival for patients treated by gemcitabine alone
Time Frame: 1 year
Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST v1.1) or death (from any cause), whichever occurs first
1 year
2-year progression-free survival for patients treated by berzosertib in association with gemcitabine
Time Frame: 2 years
Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST v1.1) or death (from any cause), whichever occurs first
2 years
2-year progression-free survival for patients treated by gemcitabine alone
Time Frame: 2 years
Progression-free survival is defined as the delay between the start date of treatment and the date of progression (as per RECIST v1.1) or death (from any cause), whichever occurs first
2 years
1-year overall survival for patients treated by berzosertib in association with gemcitabine
Time Frame: 1 year
Overall survival is defined as the delay between the start date of treatment and the date of death (from any cause)
1 year
1-year overall survival for patients treated by gemcitabine alone
Time Frame: 1 year
Overall survival is defined as the delay between the start date of treatment and the date of death (from any cause)
1 year
2-year overall survival for patients treated by berzosertib in association with gemcitabine
Time Frame: 2 years
Overall survival is defined as the delay between the start date of treatment and the date of death (from any cause)
2 years
2-year overall survival for patients treated by gemcitabine alone
Time Frame: 2 years
Overall survival is defined as the delay between the start date of treatment and the date of death (from any cause)
2 years
6-month objective response according to CHOI criteria, independently for each arm
Time Frame: 6 months
Objective response is defined as complete response (CR) or partial response (PR) as per CHOI criteria.
6 months
Best overall response according to CHOI criteria, independently for each arm
Time Frame: throughout the treatment period, an expected average of 6 months
Best overall response is defined as the best reponse across all time points (CHOI criteria). The best overall response rate is determined once all the data for the patient is known
throughout the treatment period, an expected average of 6 months
Safety profile independently for each arm: Common Terminology Criteria for Adverse Event version 5
Time Frame: throughout the treatment period, an expected average of 6 months
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
throughout the treatment period, an expected average of 6 months
Tumor immune cells levels
Time Frame: before treatment onset and cycle 2 day 1 (each cycle is 21 days)
Levels of immune cells (CD4, CD8, PDL1)in tumor will be measured by immunohistochemistry
before treatment onset and cycle 2 day 1 (each cycle is 21 days)
Blood cytokines levels
Time Frame: baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days)
Levels of cytokines (tryptophane, interleukine) in blood will be measured by ELISA
baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days)
Blood lymphocytes levels
Time Frame: baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days)
Levels of fixed PBMC (peripheral blood mononucear cells) in blood will be measured by flow cytometry
baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days)
Blood kynurenine levels
Time Frame: baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days)
Levels of kynurenine in blood will be measured by ELISA
baseline, cycle 2 day 1, cycle 6 day 1 and progression (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut Bergonié

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 9, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 29, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 21, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 15, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 19, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IB 2018-04
  • 2018-003835-31 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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