None listed
Conditions
Brief summary
The main focus of this study it to determine if giving immune activating anti-cancer therapy (Nivolumab) is safe in kidney transplant patients with incurable cancer. Who is it for? You may be eligible to join this study if you are a recipient of renal transplant (at least 3 months post- transplant) aged 18 years or above and have been diagnosed with an incurable cancer. Study details All study participants will receive Nivolumab (3mg/kg) as an intravenous infusion over 60 minutes every 2 weeks and study treatment will continue as long as there is clinical benefit up to 2 years. Nivolumab is an antibody (a type of human protein) that is being tested to see if it will allow the body’s immune system to work against tumour cells. That is using the body’s immune reaction to destroy cancer cells. Currently kidney transplant patients are excluded from clinical trials of this anti-cancer therapy - because they are taking anti-rejection medication. This trial is about trying to decide the balance between giving anti-rejection drugs and anti-cancer therapy.
Interventions
This Phase 1, multicenter, open label, two tier safety study is designed to assess the safety of standard dosing of Nivolumab in kidney transplant patients with pretreated incurable cancer or defined metastatic solid tumours. Patient recruitment will be stratified by entry median fluorescent intensity (MFI) antibodies to donor antigens such that we envisage two tiers: patients at low immunological risk with no HLA donor specific antibodies; and intermediate immunological risk (HLA antibodies 60
This Phase 1, multicenter, open label, two tier safety study is designed to assess the safety of standard dosing of Nivolumab in kidney transplant patients with pretreated incurable cancer or defined metastatic solid tumours. Patient recruitment will be stratified by entry median fluorescent intensity (MFI) antibodies to donor antigens such that we envisage two tiers: patients at low immunological risk with no HLA donor specific antibodies; and intermediate immunological risk (HLA antibodies 600-4000 MFI). Nivolumab (3mg/kg) will be administered as an intravenous infusion over 60 minutes every 2 weeks (1 cycle) per cancer specific protocols and study treatment will continue as long as there is tumour response for up to 2 years. .
Sponsors
Central Northern Adelaide Local Health Network, Royal Adelaide Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
*Patient has provided written informed consent prior to initiation of any study specific activities/procedures. *Recipient of renal transplant aged 18 years or older more than 3 months post-transplant *Recipients of multiple renal transplants will be allowed *Incurable locally advanced or metastatic, histologically proven tumours, progressing on standard first line therapy or metastatic solid tumours requiring palliative treatment (the latter group of patients are not required to have had prior anti-cancer therapy) or in-operable tumours where standard curative treatment approaches will either have failed or are not applicable. *ECOG 0-1 and 2 by discussion with medical monitor *Disease that is measurable by RECIST *Eligible tumour types include: a. SCC of the skin b. SCC of head and neck c. Melanoma d. Merkel Cell Carcinoma e. NSCLC Lung cancer f. Urothelial cancer g. Colorectal cancer which is MSI-H . h. Breast cancer (triple negative) i. Any other solid tumour which is MSI-H j. Any tumour which is deemed to be sensitive to PD-1 blockade *Co-morbid conditions are stable *Life expectancy >3 months *Patient has adequate organ and bone marrow function within 14 days of study entry a. Neutrophil count >1.5 x109/L b. Platelets >100 x109/L c. Hb >80g/L d. Total bilirubin <1.5 upper limit of normal, (ULN) e. ALT and AST <3.0 x ULN f. Serum creatinine <1.5 x ULN g. PT and APTT <1.3 x ULN *Willing to stay on, restart or have no contraindications to immunosuppressive agents including calcineurin inhibitors, antiproliferative agents and prednisolone if deemed appropriate by the study investigators. *For females of reproductive potential-negative pregnancy test prior to study entry and use of highly effective contraception *For males of reproductive potential: use of condoms
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation: *Within 3 months of transplantation and at the time of initiation of Nivolumab. *Unable to provide informed consent *Not prepared or unable to re-join a renal dialysis program *Unable to undertake monitoring for signs of rejection, toxicity or anti-tumour effect *The patient has uncontrolled or significant intercurrent or recent illness including: a) Auto-immune disorder or uncontrolled endocrinopathy b) Cardiac disorder such as uncontrolled cardiac failure, unstable angina or NSTEMI or myocardial infarction, uncontrolled arrhythmia c) Stroke or thromboembolic event within 3 months of study commencement d) Active or uncontrolled severe infection e) Active coagulopathy/bleeding diathesis f) Cirrhosis, chronic active or untreated persistent hepatitis * The patient is pregnant or lactating * The patient doesn’t agree to use highly effective methods of contraception. * Prisoners or subjects who are involuntarily incarcerated * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness * Donor specific antibody with MFI >4000 units
Outcome results
None listed