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
- 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
- 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|
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.
|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)|
|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|
Experimental: Spartalizumab and Canakinumab
Subjects with renal cell carcinoma will receive study treatment Q4 weeks x 2 doses prior to radical nephrectomy.
Spartalizumab at 400 mg weeks x 2 doses prior to radical nephrectomy Infusion
Other Name: PDR-001
Canakinumab 300 mg IV Q4 weeks x 2 doses prior to radical nephrectomy Infusion
Other Name: ACZ885
- 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).
- 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.
- 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.
- 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.
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
|Contact: Lisa Olmosemail@example.com|
|Contact: Monica Hounsellfirstname.lastname@example.org|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Lisa Olmos, RN 212-342-5162 email@example.com|
|Principal Investigator: Charles Drake, MD PhD|
|Principal Investigator:||Charles Drake, MD, PhD||Professor of Medicine and Urology|