The effect of adjuvant tislelizumab plus chemotherapy on failure free survival after post-operative pelvic chemoradiation in high risk endometrial cancer – ADELE: a randomised phase 2 trial

ACTRN 12621000273886

Brief Summary

The ADELE clinical trial seeks to improve outcomes for people with high-risk endometrial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs, who have a significant riskthe possibility that something bad will happen of relapsethe return of disease after standard post-operative treatment with chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells & radiotherapy.

Intervention/Treatment

• Pelvic chemoradiation.
• Drug: Tislelizumab.
• Drug: Carboplatin.
• Drug: Paclitaxel

Inclusion Criteria

INCLUSION CRITERIA AT REGISTRATION:

1. People aged 18 years and older, with a histological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of high-risk endometrial cancer where adjuvant chemotherapychemotherapy given after primary treatment, such as surgery, to reduce the risk of your cancer coming back is indicated. High-risk is defined as follows. Note: ECs with mixed histology will be accepted:
   • As per FIGO 2023: stage II-IVA endometrial cancer
     OR
   • As per FIGO 2018:
     1. Stage IA (with myometrial invasion) – IVA endometrial cancer with serous, clear cell, carcinosarcoma or mixed histology; or
     2. Stage III or IVA endometrial cancer with endometroid histology, any gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells; or
     3. Stage II endometrial cancer with endometroid histology, that is grade 3 or p53 abnormal by IHC or mutation testing.
2. Completed prior surgical treatment with total hysterectomycomplete or partial removal of the uterus and bilateral salpingo-oophorectomyremoval of both ovaries and fallopian tubes +/- lymph nodea small lump or mass of tissue in your body evaluation (either lymph node sampling or lymphadenectomysurgical removal of lymph node(s)) and planned for adjuvant therapy.
3. Have not received any prior chemotherapy for endometrial cancer (adjuvant pelvic chemoradiation exempted).
4. Have not received any prior pelvic radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells (adjuvant pelvic chemoradiation exempted).
5. Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status 0 or 1.
6. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
7. Signed, written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..

INCLUSION CRITERIA AT RANDOMISATION:

1. Participants with AEs as a result of pelvic chemoradiation must have recovered to baseline or at least Grade 1 as per CTCAE v5.0. Note: participants with the following AEs that are not considered a safety risk by investigator are exempted and may proceed to randomisation: alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness or isolated laboratory abnormalities that are not clinically significant.
2. Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function:
   • Haemoglobin greater or equal to 90 g/L.
   • Absolute neutrophil count greater or equal to 1.5 x 10^9/L.
   • Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding greater or equal to 100 x 10^9/L.
3. Adequate liver function:
   • Alanine transaminase lesser or equal to 2.5 x upper limit of normal (ULN).
   • Aspartate aminotransferase lesser or equal to 2.5 x ULN.
   • Total bilirubin lesser or equal to 1.5 x ULN (except participants with Gilbert’s syndrome, who are eligible with bilirubin lesser or equal to 3 ULN).
4. Adequate renal function:
   • creatinine clearance greater or equal to 50 ml/min as per Cockcroft-Gault Equation
     OR
   • greater or equal to 50 mL/min as per measured renal nuclear glomerular filtration rate study