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Trial registered on ANZCTR


Registration number
ACTRN12621000273886
Ethics application status
Approved
Date submitted
25/11/2020
Date registered
11/03/2021
Date last updated
11/01/2024
Date data sharing statement initially provided
11/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Adjuvant tislelizumab plus chemotherapy after post-operative pelvic chemoradiation in high risk endometrial cancer
Scientific title
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
Secondary ID [1] 302600 0
ANZGOG 1910/2020
Secondary ID [2] 303072 0
CTC0299
Universal Trial Number (UTN)
Trial acronym
ADELE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Cancer 319485 0
Condition category
Condition code
Cancer 317451 317451 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 318884 0
Treatment: Drugs
Comparator / control treatment
The control group will receive a sequential adjuvant treatment of pelvic chemoradiation, followed by 4 cycles of Carboplatin plus Paclitaxel chemotherapy - dosing will be the same as the experimental group.
Control group
Active

Outcomes
Primary outcome [1] 325484 0
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.
Timepoint [1] 325484 0
12 months post randomisation
Secondary outcome [1] 388114 0
Feasibility of delivering combined adjuvant tislelizumab and carboplatin plus paclitaxel chemotherapy after post-operative pelvic chemoradiation for high-risk EC. Feasibility is defined by the proportion of of participants who received at least two thirds of their prescribed number of cycles of their allocated treatment.

Study database will record the number of participants who received at least two thirds of their prescribed number of cycles in their allocated treatment as all participant visits and treatment will be documented.
Timepoint [1] 388114 0
Two thirds or more of the prescribed number of cycles in experimental group is defined as:
i) completed 3 or more cycles of chemotherapy and tislelizumab
ii) completed 8 or more cycles tislelizumab (of the planned total of 12)

Outcome will be assessed after all participants have completed treatment.
Secondary outcome [2] 388115 0
Failure free survival time at 6 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.
Timepoint [2] 388115 0
6 months post randomisation
Secondary outcome [3] 388116 0
Overall survival time assessed using patient medical chart.
Timepoint [3] 388116 0
From the date of randomisation to date of death from any cause
Secondary outcome [4] 388117 0
Frequency and severity of treatment-related adverse events as per CTCAE v5.0 assessed using patient medical chart
Timepoint [4] 388117 0
Duration of the trial
Secondary outcome [5] 391651 0
Failure rate at 6 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.
Timepoint [5] 391651 0
6 months post randomisation
Secondary outcome [6] 392725 0
EORTC QLQ-C30 to measure patients' physical, psychological and social functions.
Timepoint [6] 392725 0
12 months post randomisation
Secondary outcome [7] 392726 0
QLQ-CIPN to assess peripheral neuropathy
Timepoint [7] 392726 0
12 months post randomisation
Secondary outcome [8] 392727 0
FACIT TS-G to obtain an overall evaluation of current treatment in chronic illnesses
Timepoint [8] 392727 0
12 months post randomisation
Secondary outcome [9] 392728 0
EQ-5D-5L is a scale that measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression
Timepoint [9] 392728 0
12 months post randomisation
Secondary outcome [10] 392729 0
QLQ-EN24 to assess disease and treatment specific aspects of the quality of life of patients with endometrial cancer
Timepoint [10] 392729 0
12 months post randomisation

Eligibility
Key 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) FIGO 201835 stage IA (with myometrial invasion) - IVA endometrial cancer with serous, clear cell, carcinosarcoma or mixed histology; or
b) FIGO 2018 stage III or IVA endometrial cancer with endometroid histology, any grade; or
c) FIGO 2018 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
4) Have not received any prior pelvic radiation therapy
5) Adequate bone marrow function
• Haemoglobin greater or equal to 90 g/L
• Absolute neutrophil count greater or equal to 1.5 x 109/L
• Platelets greater or equal to 100 x 109/L
6) 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
7) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 3)
8) Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
9) Signed, written informed consent
4.3 Inclusion Criteria at Randomisation
10) 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.
11) Adequate bone marrow function
• Haemoglobin greater or equal to 90 g/L
• Absolute neutrophil count greater or equal to 1.5 x 109/L
• Platelets greater or equal to 100 x 109/L
12) Adequate liver function
• Alanine transaminase lesser or equal to 2.5 x upper limit of normal (ULN)
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• 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)
13) 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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:
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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) Pulmonary embolism lesser or equal to 28 days before randomisation
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/07/2022
Actual
3/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
135
Accrual to date
28
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 18246 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 18247 0
Royal Hospital for Women - Randwick
Recruitment hospital [3] 18248 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 18249 0
The Royal Women's Hospital - Parkville
Recruitment hospital [5] 18657 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [6] 25987 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [7] 25988 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [8] 25989 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [9] 25990 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [10] 25991 0
Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [11] 25992 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [12] 25993 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [13] 25994 0
Frankston Hospital - Frankston
Recruitment hospital [14] 25995 0
The Townsville Hospital - Douglas
Recruitment postcode(s) [1] 32310 0
2031 - Randwick
Recruitment postcode(s) [2] 41841 0
2050 - Camperdown
Recruitment postcode(s) [3] 41838 0
2298 - Waratah
Recruitment postcode(s) [4] 32311 0
3000 - Melbourne
Recruitment postcode(s) [5] 32312 0
3052 - Parkville
Recruitment postcode(s) [6] 37896 0
3168 - Clayton
Recruitment postcode(s) [7] 41843 0
3199 - Frankston
Recruitment postcode(s) [8] 41840 0
4029 - Herston
Recruitment postcode(s) [9] 41844 0
4814 - Douglas
Recruitment postcode(s) [10] 37895 0
5000 - Adelaide
Recruitment postcode(s) [11] 41839 0
5042 - Bedford Park
Recruitment postcode(s) [12] 41842 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 26069 0
New Zealand
State/province [1] 26069 0
Auckland
Country [2] 26070 0
New Zealand
State/province [2] 26070 0
Wellington

Funding & Sponsors
Funding source category [1] 307027 0
Government body
Name [1] 307027 0
Australian Government - Medical Research Future Fund (MRFF)
Country [1] 307027 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney, Camperdown, NSW 2006
Country
Australia
Secondary sponsor category [1] 308510 0
None
Name [1] 308510 0
Address [1] 308510 0
Country [1] 308510 0
Other collaborator category [1] 281517 0
Other Collaborative groups
Name [1] 281517 0
Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Address [1] 281517 0
Level 6, Chris O’Brien Lifehouse
119-143 Missenden Road,
Camperdown, NSW 2050
Country [1] 281517 0
Australia
Other collaborator category [2] 282037 0
Individual
Name [2] 282037 0
Professor Linda Mileshkin (Chief Principal Investigator)
Address [2] 282037 0
NHMRC Clinical Trials Centre Level 6, Chris O'Brien Lifehouse 119-143 Missenden Road, Camperdown NSW 2050
Country [2] 282037 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307158 0
Sydney Local Health District (SLHD) - RPA Zone Research Ethics and Governance
Ethics committee address [1] 307158 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
Camperdown, NSW 2050
Ethics committee country [1] 307158 0
Australia
Date submitted for ethics approval [1] 307158 0
24/11/2020
Approval date [1] 307158 0
22/12/2020
Ethics approval number [1] 307158 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes
Professor Linda Mileshkin and Dr Yeh Chen Lee are joint principal investigators for this trial

Contacts
Principal investigator
Name 106234 0
Dr Yeh Chen Lee
Address 106234 0
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119-143 Missenden Road,
Camperdown NSW 2050
Country 106234 0
Australia
Phone 106234 0
+61 2 9562 5392
Fax 106234 0
Email 106234 0
yehchen.lee@health.nsw.gov.au
Contact person for public queries
Name 106235 0
Ms Claire Niu (ADELE Clinical Trial Project Manager)
Address 106235 0
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119-143 Missenden Road,
Camperdown NSW 2050
Country 106235 0
Australia
Phone 106235 0
+61 2 9562 5304
Fax 106235 0
Email 106235 0
ADELE.study@sydney.edu.au
Contact person for scientific queries
Name 106236 0
Ms Claire Niu (ADELE Clinical Trial Project Manager)
Address 106236 0
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119-143 Missenden Road,
Camperdown NSW 2050
Country 106236 0
Australia
Phone 106236 0
+61 2 9562 5304
Fax 106236 0
Email 106236 0
ADELE.study@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Currently no plan and participant informed consent will be required.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.