Metastatic renal cell carcinoma Cancer
Conditions
Interventions
This is a single arm study
All participants will receive nivolumab 3mg/kg plus ipilimumab 1mg/kg intravenously, every 3 weeks, x4 cycles
This will be followed by single agent nivolumab, 480mg IV or 12
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 years or above 2. Diagnosed with metastatic RCC 3. Histologically confirmed clear cell renal cell carcinoma (or a component of clear cell) 4. Intermediate- or poor-risk disease according to IMDC classification 5. Evidence of measurable disease as per RECIST v1.1 6. Karnofsky score at least 70% 7. Eligible and planned for standard of care immunotherapy (nivolumab + ipilimumab) 8. Required laboratory values within 14 days prior to C1D1: a. WBC = 2 × 10?/L b. Neutrophils = 1.5 × 10?/L c. Platelets = 100 × 10?/L d. Haemoglobin > 9.0 g/dL e. Serum creatinine = 1.5 × ULN or calculated creatinine clearance (CrCl) = 40 mL/min (Wright formula) f. ALT = 3 × ULN g. Total Bilirubin = 1.5 × ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 50 µmol/L) 9. Tumour lesion amenable to cryoablation in the opinion of the investigator (if a metastasis is ablated, at least one other measurable lesion must be present) 10. Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 5 months thereafter 11. Participant is able (in the Investigator’s opinion) and willing to comply with all study requirements 12. Participant willing to allow their General Practitioner and consultant to be notified of participation in the study 13. Participant is willing and able to provide written informed consent for the study
Exclusion criteria
Exclusion criteria: 1. Female participant who is pregnant, lactating, or planning pregnancy during the study. - Negative serum pregnancy test required for females of childbearing potential at screening and to be reconfirmed 24 hours pre-treatment. 2. Participant is enrolled in another investigational trial and/or is taking investigational medication and/or has been treated with an investigational device =30 days prior to planned procedure date. 3. In the Investigator’s opinion, the participant has co-morbid disease(s) or condition(s) that would cause undue risk and preclude safe use of the Cryocare Touch system. 4. Prior systemic therapy for metastatic RCC (mRCC). 5. Prior adjuvant immunotherapy for RCC at any time. 6. Participant has a concurrent condition that, in the Investigator’s opinion, could jeopardize the safety of the subject or compliance with the protocol. 7. Participants who test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection. 8. Participants who test positive for human immunodeficiency virus (HIV) or have known acquired immunodeficiency syndrome (AIDS). 9. Active, known, or suspected autoimmune disease. - Subjects are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. 10. Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab or ipilimumab. - Exceptions: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection) b. Systemic corticosteroids at physiologic doses c. Steroids as premedication for hypersensitivity reactions 11. Major surgical procedure within 28 days prior to the first dose of immunotherapy. 12. Unable to undergo general anaesthesia (e.g., allergies to anaesthesia or history of adverse reactions to anaesthesia). 13. Untreated brain metastases or brain metastases treated only with whole brain radiotherapy. - Patients are eligible if previous brain metastases were treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT), or gamma knife with no subsequent evidence of progression and are asymptomatic.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of grade 3-5 adverse events, as per CTCAE V5.0 criteria, measured continuously and for up to 100 days post cessation of trial therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Detection of immunogenic cell death, measured by plasma calreticulin ELISA, at 4-8h, 12-24h post cryo-ablation and pre-cycle 2 and pre-cycle 4 of study therapy | — |
Countries
United Kingdom
Contacts
Public ContactMarta Kurzawa
Outcome results
None listed