Randomized phase III trial in MMR deficient endometrial cancer patients comparing chemotherapy alone versus Dostarlimab in first line advanced/metastatic setting: DOMENICA STUDY (GINECO-EN105b/ENGOT-en13 study)
- Conditions
- Patients with MMR deficient relapse or advanced / metastatic endometrial cancerMedDRA version: 21.0Level: PTClassification code: 10014733Term: Endometrial cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-510097-14-00
- Lead Sponsor
- Arcagy Gineco
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 267
1. Female patient is at least 18 years of age, 10. Availability of 1 block for MMR/MSI status centralized confirmation for IHC or PCR/ NGS, and additional block(s) for Translational Research, 11. Patient could have been previously treated with hormone therapy, for the metastatic/advanced disease, 12. Patient may have received pelvic and lombo-aortic external beam +/- vaginal brachytherapy, 13. Patient has adequate organ function, defined as follows: a) Absolute neutrophil count = 1,500 cells/µL b) Platelets = 100,000 cells/µL c) Haemoglobin = 9 g/dL or = 5.6 mmol/L d) Serum creatinine = 1.5× upper limit of normal (ULN) or calculated creatinine clearance = 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN e) Total bilirubin = 1.5× ULN (= 2.0 x ULN in patients with known Gilbert’s syndrome) or direct bilirubin = 1× ULN f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5× ULN unless liver metastases are present, in which case they must be = 5× ULN GINECO-EN105b/ENGOT-en13 – DOMENICA – Protocol – Version 3.0 – 08/03/2023 (From FORM 113-02 : Protocol – Application date : 22/JUN/2020) Page 9 on 152 g) International normalized ratio or prothrombin time (PT) =1.5× ULN and activated partial thromboplastin time =1.5× ULN. Patients receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of intended use of anticoagulants, 14. Patient must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of non-childbearing potential. Non-childbearing potential is defined as follows: a) Patient is = 45 years of age and has not had menses for > 1 year. b) A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrhoeic for < 2 years without a hysterectomy and oophorectomy. c) Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation: - Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, MRI, or CT scan. - Tubal ligation must be confirmed with medical records of the actual procedure; otherwise, the patient must fulfil the criteria in Inclusion Criterion 14. - Information must be captured appropriately within the site’s source documents, 15. Patient of childbearing potential must agree to use a highly effective method of contraception (section 18.8) with their partners starting from time of consent through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient (Information must be captured appropriately within the site’s source documents)., 2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements, 3. Patient with histologically proven endometrial adenocarcinoma with recurrent or advanced disease, 4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, 5. Patient must have primary Stage IIIA to C2 or Stage IV disease or first recurrent endometrial cancer (see International Federation of Gynecology and Obstetrics staging FIGO Staging – Appendix 18.1) without curative treatment by radiation therapy or surgery alone or in combination, and meet at least one of the following situations: a) Patient has Patient has primary Stage IIIA-IIIC1 with no amenable curative intent surgery or ra
1. Patient has received neoadjuvant/adjuvant systemic chemotherapy for primary Stage III or IV disease and has had a recurrence or PD within 6 months of completing this chemotherapy treatment prior to entering the study. Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies do not exclude patients from study participation, 10. Patient has known active viral infection of hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] detection), 11. Patient has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (eg, thyroid hormone or insulin), 12. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment, 13. Patient has not recovered (ie, to Grade = 1 or to baseline) from cytotoxic therapy-induced adverse events (AEs). Note: Patients with Grade = 2 neuropathy, Grade = 2 alopecia, or Grade = 2 fatigue are an exception to this criterion and may qualify for the study, 14. Patient has not recovered adequately from AEs or complications from any major surgery prior to starting therapy, 15. Patient has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab components or excipients, 16. Patient is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment, 17. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent), 18. Use of any of the following immunomodulatory agents within 30 days prior to the first dose of study drug: ? Systemic corticosteroids (at dose higher than 10 mg/day equivalent prednisone); if systemic corticoid use at higher dose, corticoid must be stopped at least 7 days before study treatment start ? Interferons ? Interleukins ? Live vaccine Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed as other killed vaccines, if done at least 2 weeks prior the first dose of study drug; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed, 19. Patient is pregnant or breastfeeding or is expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment, or lactating woman, 2. Patient has had > 1 recurrence of endometrial cancer, treated with chemotherapy. Surgery of the recurrence is allowed, 20. Patients who had an allogenic tissue/solid organ transplant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method