A pilot study of Perindopril in combination with first line Ipilimumab and Nivolumab for patients with unresectable or metastatic melanoma- ACE-IT 001

ACTRN 12621000156886

Brief Summary

This study is investigating whether it is safe to add a bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure medication to standard immunotherapya treatment that uses a person's immune system to fight cancer treatments for metastatic melanomaa type of cancer that develops from melanocytes, which are the cells that produce pigment generally in the skin (but can develop in other areas of the body) (melanoma that has spread to other body organs or systems).

Intervention/Treatment

• Drug: Perindopril.
• Drug: Ipilimumab.
• Drug: Nivolumab.

Inclusion Criteria

1. Male or Female subjects aged 18 years or over.
2. 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..
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 cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs 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 dosethe amount of medication taken of PD-1/PD-L1 therapy.
6. 6. Adequate haematological function defined by:
   • Absolute neutrophil count equal to or greater that 1.0 x 109/L.
   • Platelet count equal to or greater than 80 x 109/L.
   • Haemoglobin equal to or greater than 9g/dL – without prior transfusion within last 28 days.
7. Adequate hepatic function defined by:
   • Total bilirubin level equal to or greater than 1.5 x ULN.
   • 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:
   • 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, Abdomenstomach, stomach area, belly, 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 metastasiswhen the cancer has spread to other parts of the body, also known as mets 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.