None listed
Conditions
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.
Interventions
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 Niv
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.
Sponsors
Calvary Mater Newcastle
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed