Adjuvant tislelizumab plus chemotherapy after post-operative pelvic chemoradiation in high risk endometrial cancer
- Conditions
- Endometrial CancerCancer - Womb (Uterine or endometrial cancer)
- Registration Number
- ACTRN12621000273886
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Female
- Target Recruitment
- 135
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 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 pu
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Failure free survival (FFS) at 12 months. Failure is defined by development of new lesions or progression of existing abnormalities thought to be due to cancer as determined by site investigator, and assessed using patient medical chart.[ 12 months post randomisation]
- Secondary Outcome Measures
Name Time Method