Nivolumab in renal transplant recipients with cancer

• Register: ANZCTR
• Last refreshed on: 7 March 2022
• Main ID: ACTRN12617000741381
• Date of registration: 22/05/2017
• Prospective Registration: Yes
• Primary sponsor: Central Northern Adelaide Local Health Network, Royal Adelaide Hospital
• Public title: Nivolumab in renal transplant recipients with cancer
• Scientific title: Nivolumab in renal transplant recipients with poor prognosis cancers - a safety study.
• Date of first enrolment: 31/08/2017
• Target sample size: 30
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12617000741381.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy;
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: A/Prof Robert Peter Carroll

• Name: A/Prof Robert Peter Carroll

Key inclusion & exclusion criteria

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

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Renal and Urogenital - Kidney disease

Cancer - Any cancer

Renal Transplant;Cancer;
Renal Transplant
Cancer

Intervention(s)

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. .

Primary Outcome(s)

Rate of irretrievable renal graft rejection in transplant recipients with solid tumours not curable using standard treatment paradigms receiving a standard schedule of Nivolumab. Renal function will be measured and any rise in creatinine deemed to be significant by the treating physician will lead to renal transplant biopsy. Complete loss of kidney function with return to dialysis is the definition of irretrievable graft loss. [2-4 cycles of Nivolumab]

Secondary Outcome(s)

Patient survival in patients treated with Nivolumab.[Up to 2 years]

Tumour response to Nivolumab in patients with incurable, locally advanced or metastatic malignancy following failure of curative treatment tumours. Tumour must be known to be potentially responsive to Nivolumab as defined by Phase II and III studies. Tumour response defined by RECIST criteria.

[Up to 2 years]

Renal allograft survival in patients treated with Nivolumab[2 years]

To determine the safety (as per NCI Common Terminology Criteria for Adverse Events (v4.03: June 14, 2010)) of Nivolumab in recipients of renal transplants.
[Up to 2 years]

Secondary ID(s)

Protocol CA209-993ISR

Source(s) of Monetary Support

Royal Adelaide Hospital Research Fund

Ethics review

Status: Approved
Approval date: 24/02/2017
Contact:

Results

• Results available: Yes
• Date Posted: 25/02/2022
• Date Completed: 01/12/2021