Renal Cancer Cancer Renal Cancer
Conditions
Interventions
Eligible participants are randomised 2:1 to one of two groups. Those in the first group receive a modified schedule of IV Ipilimumab combined with IV Nivolumab every 12 weeks (Weeks 1, 13, 25, 37) wit
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 years or over 2. Diagnosed with advanced (not amenable to curative surgery) or metastatic RCC 3. Histopathologically confirmed clear cell renal cell cancer (or with a component of clear cell) 4. Evidence of measurable disease as per RECIST v1.1 (ie, =1 malignant tumour mass that can be accurately measured in at least 1 dimension = 20 mm with conventional computerized tomography scan or Magnetic Resonance Imaging [MRI], or =10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable 5. Life expectancy of = 6 months 6. Karnofsky Performance Status (KPS) of at least 70% 7. Required laboratory values within 14 days prior to registration: 7.1. WBC = 2000/µL 7.2. Neutrophils = 1500/µL 7.3. Platelets = 100 x103/µL 7.4. Haemoglobin > 9.0 g/dL 7.5. Serum creatinine = 1.5 x ULN or calculated creatinine clearance (CrCl) = 40 mL/min (Cockcroft and Gault or Wright formula may be used according to local practice) 7.6. AST and ALT = 3 x ULN 7.7. Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) 8. Able to give written informed consent and willing to follow trial protocol 9. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug (See Appendix 2 for details). 10. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) 11. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. 12. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception
Exclusion criteria
Exclusion criteria: 1. Breast feeding 2. Prior systemic therapy for RCC (previous participation in adjuvant studies allowed, providing the patient was on the observation/placebo arm – this may require unblinding of the patient) 3. Participants who have undergone any prior systemic anti-cancer treatment, including with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways (previous participation in adjuvant studies allowed, providing the patient was on the observation/placebo arm – this may require unblinding of the patient) 4. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 5. 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 6. Participants who test positive for human immunodeficiency virus (HIV) or have known acquired immunodeficiency syndrome (AIDS) 7. Untreated brain metastases. (Patients are not eligible if brain metastases treated only with whole brain radiotherapy. Patients are eligible if previous brain metastases treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT), or gamma knife with no subsequent evidence of progression and asymptomatic. Patients are not eligible if brain metastases treated only with whole brain radiotherapy). 8. 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). 9. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. (Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease). 10. Uncontrolled adrenal insufficiency 11. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. 12. Palliative radiotherapy less than 14 days prior to first dose of study drug 13. Any history of hypersensitivity to any of the trial medications or excipients 14. Poorly controlled or serious medical or psychiatric illness that, in the Investigator’s opinion, is likely to interfere with participation and/or compliance in this clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants experiencing a grade 3/4 adverse reaction within initial 12 months of treatment as measured via adverse event (AE) reporting, where an AE has been clearly marked as an adverse reaction (AR) by the investigator. All grade 3/4 AEs judged by the investigator or sponsor as having a reasonable suspected causal relationship to nivolumab, ipilimumab or the combination of the two, will qualify as grade 3/4 ARs. AEs will be collected for all participants from the time of start of protocol treatment until 100 days post cessation of trial therapy and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events V4.03 (NCI-CTCAE), with those ARs occurring within the first 12 months of receiving the first dose of any trial drug contributing to this endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary outcome measure: Progression free survival as measured by time in days from randomisation until disease progression of death. Disease progression will be locally assessed by 12 weekly CT scans, with progression defined according to the RECIST v1.1 criteria; details of deaths occurring within the trial will be collected. The key secondary endpoint will be the proportion of patients alive and progression free at 12 months post randomisation. Secondary outcome measures: 1. Safety and toxicity as reported based on the occurrence of ARs, serious adverse events (SAEs), serious adverse reactions (SARs) and SUSARs as graded by CTCAE v4.03 and as defined in section 15.1 of the trial protocol. AEs will be collected for all participants from the time of start of protocol treatment until 100 days post cessation of trial therapy with those AEs judged by the investigator or sponsor as having a reasonable suspected causal relationship to nivolumab, ipilimumab or the combination of the two, qualifying as ARs, SARs or SUSARs as appropriate. Additionally, AEs that satisfy the seriousness criteria defined in section 15.1 of the protocol qualify as SAEs. 2. Treatment tolerability as measured by the proportion of participants experiencing a dose delay or interruption during treatment. 3. Discontinuation rates due to treatment related toxicity as measured by the proportion of participants whose treatment was discontinued specifically due to treatment-related toxicities at any point during the trial 4. Discontinuation rates due to 'other' reasons as measured by the proportion of participants whose treatment was discontinued for any reason other than treatment-related toxicities at any point during the trial 5. Overall response rate as measured by the proportion of participants who achieve either partial response or complete response (PR or CR) as their best respo | — |
Countries
England, Scotland, United Kingdom, Wales
Outcome results
None listed