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Trial registered on ANZCTR


Registration number
ACTRN12621000156886
Ethics application status
Approved
Date submitted
18/11/2020
Date registered
15/02/2021
Date last updated
15/02/2021
Date data sharing statement initially provided
15/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A study combining blood pressure medication with standard treatment in advanced melanoma. ACE-IT-001
Scientific title
A pilot study of Perindopril in combination with first line Ipilimumab and Nivolumab for patients with unresectable or metastatic melanoma- ACE-IT 001
Secondary ID [1] 302800 0
NONE
Universal Trial Number (UTN)
Trial acronym
ACE-IT001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma - Unresectable 319761 0
Melanoma - Metastatic 319762 0
Condition category
Condition code
Cancer 317696 317696 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Perindopril 2mg Oral tablet, once daily - Commencing up to 14 days prior to Immunotherapy and continuing daily throughout the duration of the study( up to 2 years).
Ipilimumab 3mg/kg Intravenous infusion every 3 weeks for 4 cycles, concurrently with Nivolumab 1mg/kg.
Nivolumab 1mg/kg Intravenous infusion every 3 weeks for 4 cycles, concurrently with Ipilimumab 3mg/kg.
Nivolumab 480mg Intravenous infusion, every 4 weeks for up to 2 years, commencing 6 weeks after the last dose of concurrent Nivolumab 1mg/kg and Ipilimumab 3mg/kg.
Perindopril will be monitored via an patient diary to check compliance.
Intervention code [1] 319081 0
Treatment: Drugs
Comparator / control treatment
No control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325738 0
To determine the Incidence of treatment related adverse events of perindopril as lead in treatment and also in combination with Ipilimumab and Nivolumab using CTCAE v5
Timepoint [1] 325738 0
Daily for the duration of the treatment (up to 2 years) and up to 30 days after treatment cessation
Secondary outcome [1] 388938 0
Overall response rate assessed by Computed Tomography imaging every 12 weeks
Timepoint [1] 388938 0
Every 12 weeks from enrolment up to 4 years post enrolment onto trial
Secondary outcome [2] 388939 0
Progression Free Survival
Progression free survival (PFS) is defined as the time difference between the baseline scan performed in screening and the first documented progression as determined by the investigator. Participants who discontinue due to any cause other than progressive disease will not be reported as progressive disease. A participant who dies of an unknown cause will be reported as progressive disease.
Timepoint [2] 388939 0
every 12 weeks during the trial and every 3 months after trial completion for 2 years.
Secondary outcome [3] 388940 0
To determine serum fibrinogen changes from baseline
Timepoint [3] 388940 0
Baseline and every 12 weeks for the duration of treatment on trial for up to 2 years
Secondary outcome [4] 388941 0
To determine if the addition of perindopril provides cardiac protection asses by transthorasic echcardiogram at baseline, after 1 months and every 3 months for 2 years
Timepoint [4] 388941 0
Baseline, week 4 and every 3 months for 12 months and then every 6 months until 24 months.

Eligibility
Key inclusion criteria
1. Male or Female subjects aged 18 years or over.
2. Written informed consent.
3. Willingness to comply with trial requirements
4. Eligible to receive Nivolumab and Ipilimumab checkpoint inhibitor as per local standard of care for the treatment of metastatic or unresectable melanoma who are treatment naïve.
5. Must not have received any prior systemic cancer therapies including but not limited to prior PD-1/PD-L1 or CTLA-4 checkpoint inhibitors. Patients who have received PD-1/PD-L1 or CTLA-4 inhibitors in the adjuvant or neo-adjuvant setting are eligible if it has been >6 months since the last dose of PD-1/PD-L1 therapy.
6. Adequate haematological function defined by:
o Absolute neutrophil count equal to or greater that 1.0 x 109/L.
o Platelet count equal to or greater than 80 x 109/L.
o Haemoglobin equal to or greater than 9g/dL – without prior transfusion within last 28 days.
7. Adequate hepatic function defined by:
o Total bilirubin level equal to or greater than 1.5 x ULN.
o AST and ALT levels equal to or greater than 2.5 x ULN unless liver metastases present then equal to or greater than 5 X ULN.
8. Adequate renal function defined by:
o Estimated creatinine clearance of greater than 40mL/min according to the Cockcroft-Gault formula.
9. Measurable disease as per RECIST 1.1 guidelines. Disease status before first treatment will be documented by contrast CT of the Chest, Abdomen, Pelvis and any known sites of disease. An MRI/CT Brain may be performed if clinically indicated at the discretion of the investigator. PET scans may be performed in addition to CT scans as per standard of care, but will not be used to assess response rates during the course of the study.
10. Presence of brain metastasis is acceptable if stability is demonstrated for at least 4 weeks prior to initiation of therapy.
11. ECOG performance status 0-2.
12. Autoimmune conditions must be stable for > 12 months prior to study entry and not require systemic immunosuppressive treatment. Topical steroid treatment for psoriasis will be allowed.
13. Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to first dose of study treatment.
14. Women must not be breastfeeding.
15. Women of childbearing potential (WOCBP) must agree to use effective contraception from the time informed consent is signed, the duration of the study and for 30 days after ceasing trial participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.
16. Males who are sexually active with WOCBP must agree to use effective contraception for the duration of the study and for 30 days after ceasing trial participation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any known condition that in the opinion of the investigator will interfere with the study results or may inflict harm on the participant.
2. Known hypersensitivity to any of the prescribed treatments.
3. Any contraindication to perindopril that is deemed significant by the treating investigator.
4. Current use of anti-hypertensive, anti-coagulation or diuretic treatments.
5. Current regular use of NSAID’s within 30 days prior to treatment.
6. Vaccination within 28 days of the first treatment dose.
7. Prior Radiation treatment within 2 weeks of planned first dose of PD-1/PD-L1 therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 307227 0
Hospital
Name [1] 307227 0
Calvary Mater Newcastle
Country [1] 307227 0
Australia
Primary sponsor type
Hospital
Name
Calvary Mater Newcastle
Address
Edith Street
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 307832 0
None
Name [1] 307832 0
Address [1] 307832 0
Country [1] 307832 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307323 0
Hunter New England Health
Ethics committee address [1] 307323 0
HNE Research Office
Level 3, Pod, HMRI,
Lot 1, Kookaburra Circuit,
New Lambton Heights NSW 2305
Ethics committee country [1] 307323 0
Australia
Date submitted for ethics approval [1] 307323 0
30/10/2020
Approval date [1] 307323 0
25/01/2021
Ethics approval number [1] 307323 0
2020/ETH02863

Summary
Brief summary
This study is investigating whether it is safe to add a blood pressure medication to standard immunotherapy treatments for metastatic melanoma (melanoma that has spread to other body organs or systems).

Who is it for?
You may be eligible for this study if you are aged 18 or older, you have been diagnosed with metastatic or unresectable melanoma, you are eligible to receive Nivolumab and Ipilimumab as per local standard of care for the treatment of melanoma, and you have not received any prior systemic (whole body) cancer therapies within the past 6 months.

Study details
All enrolled participants will be asked to take a single Perindopril oral tablet, once daily for up to 2 years. Participants will be asked to continue taking the oral tablet throughout their immunotherapy treatments which will be scheduled as:
Ipilimumab 3mg/kg intravenous infusion every 3 weeks for 4 cycles
Nivolumab 1mg/kg intravenous infusion every 3 weeks for 4 cycles
Nivolumab 480mg intravenous infusion, every 4 weeks for up to 2 years, commencing 6 weeks after the last dose of Nivolumab 1mg/kg.
You will have a blood test before each treatment to make sure it is still safe to give the treatment. Throughout the trial you will have routine CT scans of your chest abdomen and pelvis every 12 weeks to check if the cancer has shrunk or grown. You will also have a ultrasound of your heart before you commence treatment, after 1 month and then every 3 months for 2 years to make sure that there are no issues with your heart.

It is hoped this research will determine that adding perindopril to standard immunotherapy treatments for patients with melanoma is safe and effective. The results of this study may lead to improved heart health outcomes for future melanoma patients if the added medication is shown to be safe.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106830 0
Dr Andre Van der Westhuizen
Address 106830 0
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre, NSW, 2310
Country 106830 0
Australia
Phone 106830 0
+61 240143581
Fax 106830 0
+61240143287
Email 106830 0
[email protected]
Contact person for public queries
Name 106831 0
Kim Adler
Address 106831 0
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre
NSW 2310
Country 106831 0
Australia
Phone 106831 0
+61240143282
Fax 106831 0
+612 40143287
Email 106831 0
[email protected]
Contact person for scientific queries
Name 106832 0
Andre Van der Westhuizen
Address 106832 0
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre, NSW, 2310
Country 106832 0
Australia
Phone 106832 0
+61 240143581
Fax 106832 0
+61240143287
Email 106832 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.