Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

Not Recruiting

Trial ID: NCT03055013


This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with nivolumab to the usual approach of nephrectomy followed by standard post-operative follow-up and monitoring, in treating patients with kidney cancer that is limited to a certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent the cancer from returning. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.

Official Title

A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

Stanford Investigator(s)

Sandy Srinivas
Sandy Srinivas

Professor of Medicine (Oncology) and, by courtesy, of Urology


Inclusion Criteria:


   - Patients must have a renal mass consistent with a clinical stage >= T2Nx renal cell
   carcinoma (RCC) or TanyN+ RCC for which radical or partial nephrectomy is planned

   - Patients must have no clinical or radiological evidence of distant metastases (M0)
   unless the presumed M1 disease is planned to be resected/definitively treated (e.g.,
   thermal ablation, stereotactic radiation) at the same time or up to 12 weeks after the
   date of the initial procedure such that the patient is considered "no evidence of
   disease" (M1 NED)

      - Liver, bone, or brain metastases are not permitted

      - No more than 3 metastases are permitted, and all must be able to be removed or
      definitively treated within 12 weeks of the primary tumor resection

   - If histological confirmation of RCC has not been done within 12 months prior to
   randomization, patient must be willing to undergo a core biopsy for this purpose if
   randomized to Arm A

      - NOTE: This histologic confirmation can be a (1) standard of care diagnostic
      biopsy or (2) a research biopsy or a planned metastasectomy. Tissue must be
      obtained with results available prior to the neoadjuvant dose

         - Patients randomized to Arm A: core tumor biopsy must have demonstrated RCC
         of any histology, including sarcomatoid, unclassified, or "unknown
         histology" (if preoperative biopsy was uninformative) with exception below
         for non-diagnostic biopsies

         - If the biopsy performed following randomization clearly demonstrates a
         benign condition, oncocytoma or a different type of cancer that is not RCC,
         the patient is not eligible and must come off study

         - A non-diagnostic biopsy is considered a good faith effort and does not need
         to be repeated unless deemed clinically necessary by the treating

   - Patient must not have any prior systemic or local anti-cancer therapy for the current

      - Patient must not have undergone a partial nephrectomy for the current RCC

      - Patient must not have had a metastasectomy for the current RCC diagnosis unless
      performed to render patient NED (in addition to the planned nephrectomy) within 6
      months prior to the current diagnosis

      - Patient must not have received current or past antineoplastic systemic therapies
      for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or
      investigational agents for treatment of RCC

      - Patient must not have received prior treatment with an anti-PD-1, anti-PD-L1,
      anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug
      specifically targeting T-cell co-stimulation or checkpoint pathways

   - Patient must be >= 18 years of age. Because no dosing or adverse event data are
   currently available on the use of nivolumab therapy in patients < 18 years of age,
   children are excluded from this study

   - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
   or 1

   - Patient must not have a prior history of RCC that was treated with curative intent
   within the past 5 years

      - Patients with a prior RCC that was treated > 5 years before, are eligible if the
      current tumor is consistent with a new primary in the opinion of the treating

      - Patients with bilateral synchronous RCCs are eligible if they can be resected or
      definitively treated at the same time or within a 12 week window from time of
      initial nephrectomy (partial or radical) or procedure and maintain adequate
      residual renal function; the patient is not eligible if both kidneys are to be
      completely removed and subsequent hemodialysis will be required

         - Permitted forms of local therapy for second tumor:

            - Partial or radical nephrectomy

            - If kidney tumor is =< 3 cm: thermal ablation (e.g., radiofrequency
            ablation, cryoablation or stereotactic radiosurgery)

   - Patients cannot have concurrent malignancies, with the following exceptions:

      - Adequately treated basal cell or squamous cell skin cancer

      - In situ cervical cancer

         - A history of superficial Ta urothelial cancer is permitted (as long as not
         currently undergoing treatment) whereas T1 or greater disease is excluded if
         < 3 years from diagnosis; concurrent persistent disease is not permitted

         - Adequately treated stage I or II cancer from which the patient is currently
         in complete remission

         - Any other cancer and stage from which the patient has been disease-free for
         at least 3 years prior to the time of randomization and as long as they are
         not receiving any current treatment (e.g. adjuvant or maintenance systemic
         or local therapy)

         - Concurrent low risk prostate cancer on active surveillance

   - Patient must not have active known or suspected autoimmune disease. The following
   autoimmune disorders are permitted: patients with vitiligo, type I diabetes mellitus,
   controlled/stable hypo or hyperthyroidism due to autoimmune or non-autoimmune
   conditions (hormone replacement is allowed), psoriasis not requiring systemic
   treatment, or other conditions not expected to recur

   - Patient must not have any ongoing condition requiring systemic treatment with either
   corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive
   medications with the exceptions outlined below; patient must not have received any
   treatment with other immunosuppressive agents within 14 days prior to the first dose
   of study drug with the following exceptions:

      - Topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal
      replacement steroid doses > 10 mg daily prednisone or the 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: nausea, delayed-type hypersensitivity
      reaction caused by a contact allergen) is permitted

   - Patient must not have uncontrolled adrenal insufficiency

   - Patient must not have known evidence of chronic active liver disease or evidence of
   acute or chronic hepatitis B Virus (HBV) or hepatitis C (HCV); HBV and HCV testing
   must be completed within 8 weeks prior to randomization

      - NOTE: If the patient has been treated and cured, and the HCV ribonucleic acid
      (RNA) is undetectable, the patient is eligible for this study

   - Patient must not have any serious intercurrent illness, including ongoing or active
   infection requiring parenteral antibiotics

   - Patient must not have known evidence of human immunodeficiency virus (HIV) infection,
   since the effects of nivolumab on anti-retroviral therapy have not been studied; HIV
   testing is only required if past or current history is suspected

   - Patient must not have any 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

   - Patient must not have had any major surgery within 28 days prior to randomization

   - Patient must not be currently enrolled in other clinical trials testing a therapeutic

   - Patient must not have any history of severe hypersensitivity to a monoclonal antibody

   - Patient must have the ability to understand and the willingness to sign a written
   informed consent document

   - Patients must not be pregnant or breast-feeding, as the effects of nivolumab on the
   developing human fetus or in the nursing infant are unknown; all patients of
   childbearing potential must have a blood test or urine study within 2 weeks prior to
   randomization to rule out pregnancy; a patient of childbearing potential is defined as
   any woman, regardless of sexual orientation or whether they have undergone tubal
   ligation, who meets the following criteria: 1) has achieved menarche at some point 2)
   has not undergone a hysterectomy or bilateral oophorectomy; or 3) 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)

   - Patients must not expect to conceive or father children by using accepted and
   effective method(s) of contraception, as described in the informed consent form (ICF),
   or by abstaining from sexual intercourse for the duration of their participation in
   the study; patients of childbearing potential must use adequate methods to avoid
   pregnancy for 5 months after the last dose of nivolumab

   - White blood cells >= 2000/uL (within 8 weeks prior to randomization)

   - Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 8 weeks prior to randomization)

   - Platelet count >= 100,000/mm^3 (within 8 weeks prior to randomization)

   - Hemoglobin >= 9.0 g/dL (within 8 weeks prior to randomization)

   - Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine
   clearance (CrCl) >= 40mL/min (within 8 weeks prior to randomization)

   - Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have
   total bilirubin < 3.0 x ULN) (within 8 weeks prior to randomization)

   - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
   (within 8 weeks prior to randomization)


biological: Nivolumab

other: Patient Observation

other: Quality-of-Life Assessment

other: Questionnaire Administration

procedure: Nephrectomy

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sneha Mohile

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