A Pilot Study of Neoadjuvant Combination Spartalizumab and Canakinumab Prior to Radical Nephrectomy in Patients With Localized Clear Cell Renal Cell Carcinoma (SPARC-1 Trial)


Condition: Carcinoma, Renal Cell

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04028245

Sponsor: Columbia University

Phase: Early Phase 1

Eligibility:

  • Age: minimum 18 Years maximum 99 Years
  • Gender: All

Inclusion Criteria:

  • Radiographically consistent with or histologically confirmed clear cell RCC or predominantly clear cell RCC
  • Localized non-metastatic RCC T1b-T4NanyM0 or TanyN1M0)
  • Schedule to undergo either partial or radical nephrectomy as part of the treatment plan
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Age ≥ 18 years old at time of consent
  • HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes as defined by the following
  • Cluster of differentiation 4 (CD4+) T cell counts ≥ 350 cells/microliter OR undetectable HIV viral load
  • no history of AIDS-defining opportunistic infection in the last year
  • Normal organ and marrow function as defined below:
  • White blood cell count (WBC) > 3.0 K/mm3
  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
  • Platelets ≥ 100 K/mm3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum total bilirubin: ≤ 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN
  • Serum creatinine ≤ 1.5 x ULN or serum creatinine > 1.5
  • 3 x ULN if calculated
  • creatinine clearance (CrCl) is ≥ 30 mL/min
  • For patients with known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • For patients with a history of hepatitis C virus (HCV) infection, the infection must be treated and cured
  • Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
  • Willingness to use barrier contraception from the time of first dose of canakinumab and spartalizumab until 120 days after surgical intervention

Exclusion Criteria:

  • Presence of distant metastases
  • Presence of active, known or suspected autoimmune disease.
  • No patients with documented, active infections, treated or untreated, may be included in this study
  • Use of any live vaccines against infectious disease within 4 weeks of initiation ot study treatment.
  • Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways
  • Prior treatment for RCC including surgery, radiation, thermoablation, or systemic therapy
  • Surgery within 28 days of starting study treatment
  • Prior treatment with any antibody or drug targeting T cell costimulation or immune checkpoint pathways (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, etc)
  • Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. Note: Topical, inhaled, nasal and ophthalmic steroids are allowed
  • Allogenic bone marrow or solid organ transplant
  • History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction
  • History or current interstitial lung disease or non-infectious pneumonitis requiring the use of home oxygen
  • History of severe hypersensitivity reaction to other monoclonal antibodies
  • Current signs or symptoms of severe progressive or uncontrolled, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or cardiac disease other than directly related to RCC
  • Positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA)
  • History of known or suspected autoimmune disease with the following exceptions:
  • Vitiligo
  • Resolved childhood atopic dermatitis
  • Psoriasis (with exception of psoriatic arthritis) not requiring systemic treatment (within the past 2 years).
  • Patients with Grave's disease or Hashimoto's thyroiditis that are now euthyroid clinically and by laboratory testing.
  • History of malignancy within the last 2 years, with the exception of non-melanoma skin cancers and superficial bladder cancer
  • Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate

View trial on ClinicalTrials.gov