pReOperative Dostarlimab and Novel Therapies in EndOmetrial Cancer

A regiszterben nem jelölt feltételek

• Patient is at least 18 years of age.
• Patient is able to provide informed consent and able to comply with treatment and follow up schedule.
• Patients with surgically operable FIGO (2009) stage 3-4 endometrial cancer.
• Must not have received any systemic anti-cancer treatment (including chemotherapy, hormonal therapy, immunotherapy, surgical intervention, radiotherapy) for the current diagnosis of endometrial cancer.
• Histological diagnosis of advanced epithelial endometrial cancer (excluding carcinosarcoma).
• CT or MRI proven disease (measurable or non-measurable).
• Willing to provide tissue from archival diagnostic sample, a newly obtained core or excisional biopsy of a tumour lesion at screening and also collection of tissue during surgery.
• Mismatch repair status must be known at time of enrolment. Patients can be screened based on local MMR/MSI testing results using immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) performed in a certified local laboratory, i. MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR; dMMR may be determined locally.
  • MSI status as determined by polymerase chain reaction (PCR) or by tissue Next generation sequencing (NGS).
  • Note: Patients who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) and have dMMR or MSI-H in the tumour are eligible to participate.
• Patient must have a negative serum pregnancy test within 24 hours prior to the date of the first dose of trial medication; unless they are of non-childbearing potential.
  • Non-childbearing potential is defined as:
  • ≥ 45 years of age and has not had menses for > 1 year. ii. Amenorrheic for < 2 years without a hysterectomy and oophorectomy and have a follicle-stimulating hormone (FSH) value in the postmenopausal range upon pre-trial evaluation.
• Patients should have adequate bone marrow and laboratory functions defined as:
  • Absolute neutrophil count (ANC) ≥1.5×109/L
  • Haemoglobin ≥9 g/dL ≥5.6 mmol/L
  • Platelets ≥100×109/L
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN
  • Bilirubin ≤1.5×ULN (isolated bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)
  • For patients not taking warfarin: International normalized ratio (INR) <1.5 or prothrombin time (PT) <1.5×ULN and partial thromboplastin (PTT) <1.5×ULN. Patients taking warfarin may be included on a stable dose with a therapeutic INR <3.5.
  • Renal function parameters of GFR ≥30 mL/min/1.73m2 (institutional creatinine ≤1.5×ULN)
  • Albumin > 30
• ECOG Performance Status 0 or 1.
• Life expectancy of at least 3 months.