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A Study of Combination Spartalizumab and Canakinumab in Patients With Localized Clear Cell Renal Cell Carcinoma (SPARC-1)

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ClinicalTrials.gov Identifier: NCT04028245
Recruitment Status : Recruiting
First Posted : July 22, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Charles G. Drake, Columbia University

Brief Summary:

Primary Objective:

  • To confirm the safety and feasibility of canakinumab and spartalizumab (PDR-001) administered using a standard dose / schedule in the neo-adjuvant setting in renal cell carcinoma

Secondary Objectives:

  • To assess the immune response to combination canakinumab and spartalizumab
  • To assess anti-tumor activity as measured by pathologic downstaging

Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Drug: Spartalizumab Drug: Canakinumab Early Phase 1

Detailed Description:

Patients with localized and non-metastatic Renal Cell Carcinoma (RCC) represent an "at-need" population who would benefit from immunotherapy earlier in their disease course with a PD-1 therapy combined with a second immunotherapy agent. A logical next step is to pursue the combination of an anti-PD1 therapy with CTLA-4 blockade extrapolating from recent successes in the metastatic setting. The primary concern with previous approaches and studies is that CTLA-4 based therapy is associated with increased risk of autoimmune side effects which potentially could delay a curative surgery. Clearly, the neoadjuvant setting in RCC represents an ideal space to evaluate novel I/O combination strategies aside from CTLA-4 blockade.

This study intends to confirm the safety and feasibility of canakinumab and spartalizumab (PDR-001) administered using a standard dose / schedule in the neo-adjuvant setting in renal cell carcinoma. This is a single-center, single arm, open-label pilot study evaluating the feasibility, safety, anti-tumor effect, and immunogenicity of neoadjuvant canakinumab and spartalizumab given prior to radical nephrectomy in patients with localized renal cell carcinoma. Patients will be recruited from the outpatient Urology clinic.

Eligible patients will receive canakinumab at a dose of 300 mg Q4weeks and spartalizumab at 400 mg Q4weeks IV. Approximately 14 days after the last dose of canakinumab and spartalizumab, patients with proceed to radical nephrectomy, and nephrectomy tissue will be examined for the secondary endpoints. Follow-up evaluation for adverse events will occur 30 days and 90 days after surgery. Patients will then be followed by their urologists and oncologist according to standard institutional practices, but will require repeat labs every 3 months along with standard of care surveillance imaging.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a pilot study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Spartalizumab and Canakinumab
Subjects with renal cell carcinoma will receive study treatment Q4 weeks x 2 doses prior to radical nephrectomy.
Drug: Spartalizumab
Spartalizumab at 400 mg weeks x 2 doses prior to radical nephrectomy Infusion
Other Name: PDR-001

Drug: Canakinumab
Canakinumab 300 mg IV Q4 weeks x 2 doses prior to radical nephrectomy Infusion
Other Name: ACZ885




Primary Outcome Measures :
  1. Percentage of subjects who proceed to radical nephrectomy [ Time Frame: 6 Weeks ]
    Feasibility of spartalizumab and canakinumab will be met if > 85% of patients proceed to radical nephrectomy (12 of 14).


Secondary Outcome Measures :
  1. Quantification of CD8 T cell infiltration into the tumor / peritumoral area infiltrates [ Time Frame: 6 Weeks ]
    To assess the immune response to combination canakinumab and spartalizumab. Tumor blocks and/or additional unstained slides will be collected for study-specific quantitative immunohistochemical evaluations. Cell infiltration into the kidney resection specimens will be quantified using immunohistochemical staining methods.

  2. Quantification of immune cell populations (PMN-MDSC) in the tumor/ peritumoral area [ Time Frame: 6 Weeks ]
    To assess the immune response to combination canakinumab and spartalizumab. Tumor blocks and/or additional unstained slides will be collected for study-specific quantitative immunohistochemical evaluations. Cell infiltration into the kidney resection specimens will be quantified using immunohistochemical staining methods.

  3. Objective tumor response rate [ Time Frame: 6 Weeks ]
    To assess the immune response to combination canakinumab and spartalizumab. By RECIST and by iRC, proportion of pathCR (pT0) and downstaging (decrease in size from baseline scans) will be calculated.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed clear cell or predominantly clear cell RCC
  • Non-metastatic (localized) RCC that is clinical stage T2 and above, or clinical N1 disease with any T stage
  • Schedule to undergo either partial or radical nephrectomy as part of the treatment plan
  • ECOG 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

    • 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 ULN
    • ALT and 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
  • 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 3 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
  • Known prior or current history of HIV and/or hepatitis B/C

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028245


Contacts
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Contact: Lisa Olmos 212.342.5162 cancerclinicaltrials@cumc.columbia.edu
Contact: Monica Hounsell md3538@cumc.columbia.edu

Locations
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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Lisa Olmos, RN    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Charles Drake, MD PhD         
Sponsors and Collaborators
Charles G. Drake
Novartis
Investigators
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Principal Investigator: Charles Drake, MD, PhD Professor of Medicine and Urology

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Responsible Party: Charles G. Drake, Professor of Medicine and Urology, Columbia University
ClinicalTrials.gov Identifier: NCT04028245     History of Changes
Other Study ID Numbers: AAAS2814
First Posted: July 22, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs