A randomised phase II trial comparing two different ways of combining nivolumab and ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma.

Phase 1

• Conditions: Previously untreated metastatic clear cell renal cell carcinoma.; MedDRA version: 20.0Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10067946Term: Renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001476-33-GB
• Lead Sponsor: niversity of Leeds

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-10
• Last Update Posted: 14 May 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

•Aged 18 years or over
•Diagnosed with advanced (not amenable to curative surgery) or metastatic RCC
•Histopathologically confirmed clear cell renal cell cancer (or with a component of clear cell)
•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
•Life expectancy of = 6 months
•Karnofsky Performance Status (KPS) of at least 70%

•Required laboratory values within 14 days prior to registration:

oWBC = 2000/µL
oNeutrophils = 1500/µL
oPlatelets = 100 x103/µL
oHaemoglobin > 9.0 g/dL
oSerum 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)
oAST and ALT = 3 x ULN
oTotal Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
•Able to give written informed consent and willing to follow trial protocol
•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 A for details).
•Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
•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 (see Appendix A for details).
•Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 89

Exclusion Criteria

Participants meeting any of the following exclusion criteria are not eligible to enrol in this trial.
•Breast feeding
•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)

•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)
•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.
•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
•Participants who test positive for human immunodeficiency virus (HIV) or have known acquired immunodeficiency syndrome (AIDS)
•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).

•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).
•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).
•Uncontrolled adrenal insufficiency
•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.
•Palliative radiotherapy less than 14 days prior to first dose of study drug
•Any history of hypersensitivity to any of the trial medications or excipients
•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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified