Overview

Targeting ATR in Soft-tissue Sarcomas

Status:
Not yet recruiting
Trial end date:
2025-04-01
Target enrollment:
0
Participant gender:
All
Summary
Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of berzosertib in association with gemcitabine
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Institut Bergonié
Collaborator:
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Treatments:
Gemcitabine
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.