Targeting ATR in Soft-tissue Sarcomas
Targeting ATR in Soft-tissue Sarcomas: a Randomized Phase II Study. TARSARC Study
This study is testing if adding a new drug called berzosertib to the standard treatment gemcitabine can help people with advanced leiomyosarcoma who haven't had success with other treatments.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 72 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Institut Bergonié Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, prednisone |
| Locations | 6 sites (Bordeaux and 5 other locations) |
| Trial ID | NCT04807816 on ClinicalTrials.gov |
What this trial studies
This clinical trial is a multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial designed to evaluate the antitumor activity of berzosertib in combination with gemcitabine in patients with advanced or metastatic leiomyosarcoma. Participants will be randomly assigned to receive either gemcitabine alone or gemcitabine in conjunction with berzosertib. The trial aims to assess the efficacy of this combination therapy in patients who have not responded to previous treatments. The study will also involve the collection of tumor biopsies to monitor treatment response.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed metastatic or unresectable locally advanced leiomyosarcoma.
Not a fit: Patients who have already received more than three lines of systemic therapy for advanced disease or those who are candidates for other approved therapies may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced leiomyosarcoma who have limited treatment choices.
How similar studies have performed: While there have been studies targeting ATR in various cancers, this specific combination approach in soft-tissue sarcomas is relatively novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Bordeaux and 5 other locations
- Institut Bergonié — Bordeaux, France (Recruiting)
- Centre Leon Berard — Lyon, France (Recruiting)
- CHU Poitiers — Poitiers, France (Recruiting)
- Institut de Cancérologie de l'Ouest — Saint-Herblain, France (Withdrawn)
- IUCT Oncopôle — Toulouse, France (Recruiting)
- Institut Gustave Roussy — Villejuif, France (Recruiting)
Study contacts
- Study coordinator: Antoine ITALIANO, MD, PhD
- Email: a.italiano@bordeaux.unicancer.fr
- Phone: (0)5.56.33.33.33
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.