Ensayos clínicos

Inclusion Criteria:

ELIGIBILITY CRITERIA FOR PREREGISTRATION (STEP 0): 

• Preoperative biopsy for confirmation of renal cell carcinoma (RCC) must be performed within four (4) months prior to randomization. 
• If biopsy was performed as part of patients standard care, and will not be performed during step 0 proceed directly to randomization.

ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1): 

• Patients with newly diagnosed higher risk RCC of any histology including sarcomatoid or (if preoperative biopsy was uninformative) - "unknown" histology; RCC must have been confirmed by biopsy within 4 months prior to randomization; if the biopsy clearly demonstrated a benign condition or a different type of cancer, the patient is not eligible to be randomized - Clinical stage >= T2NxM0 or TanyN+ disease for which radical or partial nephrectomy is planned.
• Patients must have no clinical or radiological evidence of distant metastases (M0.) 
• No concurrent or prior systemic or local anti-cancer therapy for RCC is permitted; examples of these prohibited therapies include: 
  • Radical or partial nephrectomy for prior RCC;
  • Metastectomy for RCC; 
  • Radiation therapy to the renal bed or any distant metastatic sites; 
  • Antineoplastic systemic therapies for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or investigational agents for treatment of RCC; 
  • Prior treatment with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 
• Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1. 
• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 
  • Has not undergone a hysterectomy or bilateral oophorectomy; or 
  • Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential and sexually active males must be strongly advised to use accepted and effective methods of contraception, as described in the informed consent form (ICF), or to abstain from sexual intercourse for the duration of their participation in the study; women of childbearing potential should use adequate methods to avoid pregnancy for 23 weeks after the last dose of nivolumab; sexually active males should use adequate methods to avoid pregnancy for 31 weeks after the last dose of nivolumab.
• Patient must have no prior history of RCC that was resected with curative intent within the past 5 years.
• Patients must not have other current malignancies: 
  • Adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 3 years prior to the time of registration and they are not receiving any current treatment;
  • Prior or current prostate cancer is excluded;
    • A history of superficial Ta urothelial cancer is permitted (not being currently treated) but T1 or greater disease is excluded.
• No active known or suspected autoimmune disease; the following are permitted: patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune or non-autoimmune condition requiring hormone replacement, asymptomatic hypothyroidism not requiring treatment, psoriasis not requiring systemic treatment, or conditions not expected to recur.
• No ongoing condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications; no treatment with other immunosuppressive agents within 14 days prior to the first dose of study drug; topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.; a brief (less than 3 weeks) course of corticosteroids (any amount) for prophylaxis (for example: contrast dye allergy) or for treatment of non-autoimmune conditions (for example: delayed-type hypersensitivity reaction caused by a contact allergen) is permitted if > 14 days since last dose.'
• No uncontrolled adrenal insufficiency.
• No known chronic active liver disease or evidence of acute or chronic hepatitis B virus (HBV) or hepatitis C (HCV).
• Patients must not have a serious intercurrent illness, including ongoing or active infection requiring parental antibiotics.
• No known evidence of human immunodeficiency virus (HIV) infection.
• No known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results.
• No major surgery within 28 days prior to randomization.
• Patients currently enrolled in other clinical trials testing a therapeutic intervention.
• Patients must have the following baseline laboratory values within 4 weeks of randomization:
  • White blood cells >= 2000/uL, within 4 weeks of randomization.
  • Absolute granulocyte count (AGC) >= 1,500/mm^3, within 4 weeks of randomization.
  • Platelet count >= 100,000/mm^3, within 4 weeks of randomization.
  • Hemoglobin >= 9.0 g/dL, within 4 weeks of randomization.
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 40 mL/min, within 4 weeks of randomization.
  • Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 x ULN), within 4 weeks of randomization.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN, within 4 weeks of randomization.
• No history of severe hypersensitivity to a monoclonal antibody.
• Signed, dated informed consent.

Exclusion Criteria:

• None.