None listed
Conditions
Brief summary
The ADELE clinical trial seeks to improve outcomes for people with high-risk endometrial cancer, who have a significant risk of relapse after standard post-operative treatment with chemotherapy & radiotherapy. Who is it for? You may be eligible for this study if you are aged 18 or older, have been diagnosed with high-risk endometrial cancer, have completed prior surgical treatment with total hysterectomy, have not received any prior chemotherapy or pelvic radiotherapy, and are planned for adjuvant chemoradiation. Study details Participants will be randomly (by chance) assigned to one of two groups. One group will receive a sequential adjuvant treatment of pelvic chemoradiation, followed by 4 cycles of the new combination therapy with Tislelizumab and carboplatin plus paclitaxel chemotherapy, followed by Tislelizumab for another 8 cycles. The other group will receive the same treatment (standard treatment) without the addition of Tislelizumab. Participants will be followed up for 12 months to assess for relapse of endometrial cancer and symptoms of treatment. It is hoped that this study may improve relapse rates in high-risk endometrial cancer by adding Tislelizumab immunotherapy to standard treatment.
Interventions
The experimental group will receive a sequential adjuvant treatment of pelvic chemoradiation, followed by 4 cycles of tislelizumab and carboplatin plus paclitaxel chemotherapy, followed by tislelizumab alone for another 8 cycles.
Tislelizumab 200 mg will be administered via an intravenous infusion once every 3 weeks for up to 12 cycles, and carboplatin (AUC 5) and paclitaxel (175 mg/m^2) will also be administered via an intravenous infusion once every 3 weeks for up to 4 cycles and as per local
The experimental group will receive a sequential adjuvant treatment of pelvic chemoradiation, followed by 4 cycles of tislelizumab and carboplatin plus paclitaxel chemotherapy, followed by tislelizumab alone for another 8 cycles. Tislelizumab 200 mg will be administered via an intravenous infusion once every 3 weeks for up to 12 cycles, and carboplatin (AUC 5) and paclitaxel (175 mg/m^2) will also be administered via an intravenous infusion once every 3 weeks for up to 4 cycles and as per local institution guidelines). Pelvic chemoradiation should commence within 4-6 weeks after surgery, but no later than 8 weeks of surgery, and prior to chemotherapy +/- immunotherapy. Pelvic chemoradiation will be at a dose of 45Gy in 25 fractions, delivered to the clinical target volume, 5 days a week for 5 weeks.
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
INCLUSION CRITERIA AT REGISTRATION: 1) People aged 18 years and older, with a histological diagnosis of high-risk endometrial cancer where adjuvant chemotherapy is indicated. High-risk is defined as follows. Note: ECs with mixed histology will be accepted. a) As per FIGO 2023: stage II-IVA endometrial cancer OR b) As per FIGO 2018: i) stage IA (with myometrial invasion) - IVA endometrial cancer with serous, clear cell, carcinosarcoma or mixed histology; or ii) stage III or IVA endometrial cancer with endometroid histology, any grade; or iii) 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 hysterectomy and bilateral salpingo-oophorectomy +/- lymph node evaluation (either lymph node sampling or lymphadenectomy) 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 therapy (adjuvant pelvic chemoradiation exempted) 5) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 3) 6) Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments 7) Signed, written informed consent INCLUSION CRITERIA AT RANDOMISATION: 8) 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: alopecia or isolated laboratory abnormalities that are not clinically significant. 9) Adequate bone marrow function • Haemoglobin greater or equal to 90 g/L • Absolute neutrophil count greater or equal to 1.5 x 10^9/L • Platelets greater or equal to 100 x 10^9/L 10) 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) 11) 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
Exclusion criteria
EXCLUSION CRITERIA AT REGISTRATION AND RANDOMISATION: 1) Metastatic disease on CT imaging. However, patients with positive surgical margins or residual nodal disease that can be encompassed within the radiotherapy field for treatment with curative intent are eligible. 2) Uterine sarcoma (apart from carcinosarcoma) 3) Active autoimmune disease or history of autoimmune disease that may deteriorate or relapse when receiving an immunostimulatory agent (Appendix 5). Note: participants with the following conditions are not excluded and may proceed subject to further screening: a) autoimmune skin disease not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia) b) controlled type 1 diabetes mellitus c) hypothyroidism (managed with hormone replacement therapy only) 4) Any contraindications to receiving platinum and paclitaxel chemotherapy or pelvic radiation or immune checkpoint inhibitor. 5) Serious medical or psychiatric conditions that may prevent compliance with the protocol or compromise assessment of key outcomes of the study 6) Participants with other active invasive malignancies, except for non-melanoma skin cancer, or in situ melanoma, or a solid tumour treated with curative intent and no evidence of disease recurrence for more than 3 years. 7) Any condition that required systemic treatment with either corticosteroids (>10mg daily of prednisone or equivalent) or other immunosuppressive medication lesser or equal to 14 days before randomisation Note: participants who are currently or have previously been on any of the following steroid regimens are not excluded: a) Adrenal replacement steroid (dose lesser or equal to 10 mg daily of prednisone or equivalent) b) Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption c) Short course (lesser or equal to 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen) or as supportive medication for before and after chemotherapy 8) Active hepatitis B or hepatitis C virus infection 9) A known history of HIV infection 10) Known history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc. 11) Significant acute or chronic infections including but not limited to: Confidential ANZGOG1910/2020 / CTC0299 - ADELE Page 23 of 75 Version 3.0, 26 May 2023 a) Participants with active tuberculosis (history of exposure or history of positive tuberculosis test; plus presence of clinical symptoms, physical, or radiographic findings). b) Participants with active bacterial or fungal or viral infection requiring systemic therapy c) Participants with active COVID-19 infection 12) Prior allogeneic stem cell transplantation or organ transplantation 13) Any of the following cardiovascular conditions: a) Unstable angina b) Any history of acute myocardial infarction lesser or equal to 6 months before randomisation c) Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (Appendix 4) lesser or equal to 6 months before randomisation d) Any event of ventricular arrhythmia greater or equal to Grade 2 in severity lesser or equal to 6 months before randomisation e) Any history of cerebrovascular accident lesser or equal to 6 months before randomisation f) Unstable pulmonary embolism lesser or equal to 28 days before randomisation. Patient treated with therapeutic anticoagulation is acceptable on trial. 14) Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. 15) Receipt of live attenuated vaccination within 30 days prior to randomisation.
Outcome results
None listed