Endometrial Cancer Clinical Trials

• Histologically confirmed diagnosis of EC (all grades and the following histologic subtypes : endometrioid, serous, clear cell, de-/undifferentiated carcinomas, and uterine carcinosarcoma).

• Molecular classification performed following the diagnostic algorithm described in WHO 2020 (adapted from Vermij et al.)

• TLH-BSO or TAH-BSO with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after surgery

• No distant metastases as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis or PET-CT scan)

• Written informed consent prior to any study specific procedures

• Age \>= 18 years

• Patients must have a life expectancy ≥ 16 weeks

• Patients must be accessible for treatment and follow-up

• Written informed consent for one of the RAINBO trials and the overarching research project according to the local Ethics Committee requirements.

• WHO Performance score 0-1

• Histologically confirmed Stage I to III EC with myometrial invasion

• Molecular classification: p53abn EC\*

• Body weight \> 30 kg

• Patient must receive or have received a sequential radiotherapy and chemotherapy preferably given according to the PORTEC-3 regimen and should be started within 6 to 8 weeks after surgery and no later than 10 weeks: two cycles of intravenous cisplatin 50mg/m² in the first and fourth week of the pelvic external beam radiotherapy (EBRT) +/- vaginal brachytherapy followed by four cycles of intravenous carboplatin AUC 5 and paclitaxel 175 mg/m² at 21-day intervals.

⁃ However the sequence of chemotherapy , number of cycles and inclusion of cisplatin may be altered according to local practice at the investigator's discretion.

⁃ This may include;

• 4 cycles carboplatin \& paclitaxel before or after radiotherapy with 2 cycles cisplatin

• 4 cycles carboplatin \& paclitaxel before or after radiotherapy (no cisplatin)

‣ Patients registered after their standard treatment must:

⁃ provide a tumor assessment performed within the 4 weeks before the start of RT/CT. This will be considered as the M0.

⁃ have started RT/CT 6 to 8 weeks after surgery. A maximum gap of 10 weeks is accepted.

⁃ be randomized within two weeks before maintenance or observation.

⁃ Adequate systemic organ function: Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

• Creatinine clearance (\> 50 cc/min): Patients must have creatinine less than 1.5 ULN or calculated creatinine clearance estimated of ≥ 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test. Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F) / serum creatinine (mg/dL) x 72

∙ Adequate bone marrow function : hemoglobin ≥10.0 g/dl with no blood transfusion in the past 28 days, Absolute neutrophil count (ANC) ≥1.5 x 109/l, platelet count ≥ 100 x 109/l.

∙ Adequate liver function: bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.

∙ ALT (SGPT) and/or AST (SGOT) ≤2.5 x ULN

⁃ \*Molecular classification must be performed according to the diagnostic algorithm presented in the WHO 2020 (Vermij et al. 2020). For the p53abn-RED trial this means that MMR and POLE status must be determined, and must be pMMR and POLE wildtype (or non-pathogenic) for inclusion. For details on the molecular classification see 7.1: Diagnostic algorithm for molecular classification.

⁃ Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.

⁃ Patients must be affiliated to a social security system or beneficiary of the same