Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line
- Conditions
- Endometrial Cancer
- Registration Number
- NCT05201547
- Lead Sponsor
- ARCAGY/ GINECO GROUP
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Female
- Target Recruitment
- 260
Inclusion Criteria:<br><br> - Patients must fulfil all the following criteria:<br><br> 1. Female patient is at least 18 years of age,<br><br> 2. Patient has signed the Informed Consent (ICF) and is able to comply with<br> protocol requirements.<br><br> 3. Patient with histologically proven endometrial adenocarcinoma with recurrent or<br> advanced disease.<br><br> 4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status<br> score of 0 or 1.<br><br> 5. Patient must have primary Stage IIIA to C2 or Stage IV disease or first<br> recurrent endometrial cancer (see International Federation of Gynecology and<br> Obstetrics staging FIGO Staging 18.1) without curative treatment by radiation<br> therapy or surgery alone or in combination, and meet at least one of the<br> following situations:<br><br> 1. Patient has patient has primary Stage IIIA-IIIC1 with no amenable curative<br> intent surgery or radiation.<br><br> 2. Patient has first recurrent disease and is chemotherapy naïve for this 1st<br> recurrence or metastatic setting.<br><br> 3. Patient has recurrent disease and is chemotherapy naïve for recurrence or<br> advanced /metastatic setting.<br><br> 4. Patient may have received prior irradiation for advanced endometrial<br> cancer with or without radio-sensitizing chemotherapy if > 3 weeks before<br> the start of the study<br><br> 6. Patient with evaluable disease (measurable and not measurable disease)<br> according to RECIST 1.1<br><br> 7. Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy for<br> the primary cancer and had a recurrence = 6 months after completing treatment<br> (first recurrence only).<br><br> 8. All histologic subtypes of endometrial adenocarcinoma could be included if<br> MMRd/MSI-H<br><br> 9. MMRd/MSI-H tumor (first diagnosed by routine local IHC performed either on<br> primitive tumour tissue or on relapse/metastatic tumour sample) is mandatory<br> for inclusion. A central confirmation will be done before inclusion; in case of<br> ambiguous result of central IHC (lack of positive internal control,<br> heterogeneous loss of MMR protein expression), MSI-H status will be assessed by<br> PCR/NGS<br><br> 10. Availability of 1 block for MMR/MSI status centralized confirmation for IHC or<br> PCR/ NGS<br><br> 11. . Patient could have been previously treated with hormone therapy, for the<br> metastatic/advanced disease 12) Patient may have received pelvic and<br> lombo-aortic external beam +/- vaginal brachytherapy<br><br> 13. Patient has adequate organ function, defined as follows:<br><br> a) Absolute neutrophil count = 1,500 cells/µL b) Platelets = 100,000 cells/µL c)<br> Haemoglobin = 9 g/dL or = 5.6 mmol/L d) Serum creatinine = 1.5× upper limit of<br> normal (ULN) or calculated creatinine clearance = 50 mL/min using the<br> Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional<br> ULN e) Total bilirubin = 1.5× ULN (= 2.0 x ULN in patients with known Gilbert's<br> syndrome) or direct bilirubin = 1× ULN f) Aspartate aminotransferase (AST) and<br> alanine aminotransferase (ALT) = 2.5× ULN unless liver metastases are present, in<br> which case they must be = 5× ULN g) International normalized ratio or prothrombin<br> time (PT) =1.5× ULN and activated partial thromboplastin time =1.5× ULN. Patients<br> receiving anticoagulant therapy must have a PT or partial thromboplastin within the<br> therapeutic range of intended use of anticoagulants.<br><br> 14. Patient must have a negative serum pregnancy test within 72 hours of the first<br> dose of study medication, unless they are of nonchildbearing potential.<br> Nonchildbearing potential is defined as follows:<br><br> 1. Patient is = 45 years of age and has not had menses for > 1 year.<br><br> 2. A follicle-stimulating hormone value in the postmenopausal range upon screening<br> evaluation if amenorrhoeic for < 2 years without a hysterectomy and<br> oophorectomy.<br><br> 3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:<br><br> - Documented hysterectomy or oophorectomy must be confirmed with medical records of<br> the actual procedure or confirmed by an ultrasound, MRI, or CT scan.<br><br> - Tubal ligation must be confirmed with medical records of the actual procedure;<br> otherwise, the patient must fulfil the criteria in Inclusion Criterion 14.<br><br> - Information must be captured appropriately within the site's source documents. 15.<br> Patient of childbearing potential must agree to use a highly effective method of<br> contraception (section 18.9) with their partners starting from time of consent<br> through 150 days after the last dose of study treatment. Note: Abstinence is<br> acceptable if this is the established and preferred contraception for the patient<br> (Information must be captured appropriately within the site's source documents).<br><br>Exclusion Criteria:<br><br> - Patients are to be excluded from the study if they meet any of the following<br> criteria:<br><br> 1. Patient has received neoadjuvant/adjuvant systemic chemotherapy for primary<br> Stage III or IV disease and has had a recurrence or PD within 6 months of<br> completing this chemotherapy treatment prior to entering the study.<br><br> Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies<br> do not exclude patients from study participation.<br><br> 2. Patient has had > 1 recurrence of endometrial cancer, treated with<br> chemotherapy. Surgery of the recurrence is allowed.<br><br> 3. Patient previously treated with systemic chemotherapy for non-curable advanced<br> disease or metastatic disease<br><br> 4. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2<br> agent.<br><br> 5. Patient has received prior anticancer therapy for (advanced or metastatic<br> disease (targeted therapies, hormonal therapy, radiotherapy) within 21 days or<br> < 5 times the half-life of the most recent therapy prior to Study Day 1,<br> whichever is shorter Note: Palliative radiation therapy to a small field = 1<br> week prior to Day 1 of study treatment may be allowed.<br><br> 6. Patient with contraindication to chemotherapy or checkpoint inhibitor<br> treatments<br><br> 7. Patient has a concomitant malignancy, or patient has a prior non-endometrial<br> invasive malignancy who has been disease-free for < 3 years or who received any<br> active treatment in the last 3 years for that malignancy. Non-melanoma skin<br> cancer is allowed.<br><br> 8. Patient has known uncontrolled central nervous system metastases,<br> carcinomatosis meningitis, or both. Note: Patients with previously treated<br> brain metastases may participate provided they are stable (without evidence of<br> disease progression by imaging [using the identical imaging modality for each<br> assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose<br> of study treatment and any neurologic symptoms have returned to baseline), have<br> no evidence of new or enlarging brain metastases, and have not been using<br> steroids for at least 7 days
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS)
- Secondary Outcome Measures
Name Time Method