Targeting ATR in Soft-tissue Sarcomas

NCT04807816 | Completed Phase 2 DMC

• 2 other identifiers: IB 2018-042018-003835-31
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

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

Conditions

Leiomyosarcoma, Adult

Keywords

ATR inhibition; soft-tissue sarcoma; advanced/metastatic

Outcome Measures

Primary Outcomes (2)

• Assessment of the antitumor activity of berzosertib combined with gemcitabine

  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

  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 Outcomes (19)

• 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

Study Arms (2)

Experimental Arm A: treatment by berzosertib combined with gemcitabine

EXPERIMENTAL

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

Drug: Association of berzosertib with gemcitabine

Standard Arm B: treatment by gemcitabine alone

OTHER

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

Drug: Gemcitabine

Interventions

Association of berzosertib with gemcitabine 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.

Also known as: Experimental

Experimental Arm A: treatment by berzosertib combined with gemcitabine

Gemcitabine 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.

Also known as: Control

Standard Arm B: treatment by gemcitabine alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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,

Sponsors & Collaborators

• Institut Bergonié: lead
• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (5)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

CHU Poitiers

Poitiers, 86000, France

Location

IUCT Oncopôle

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Leiomyosarcoma; Sarcoma; Neoplasm Metastasis

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: March 15, 2021
• First Posted: March 19, 2021
• Study Start: February 9, 2022
• Primary Completion: September 29, 2024
• Study Completion: April 21, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)