Clinical Trials Logo

Clinical Trial Summary

This is a pilot, single-center, single-arm study where 20 patients with metastatic or unresectable clear cell renal cell carcinoma will receive same sequential treatment strategy (Cabozantinib for 12 weeks, then proceed with Ipilimumab plus Nivolumab immunotherapy x4 over 12 weeks, then subsequent therapies depending on treatment response for another 12 weeks [Nivolumab for CR/PR/SD, Cabozantinib or Lenvatinib/Everolimus for PROG]).


Clinical Trial Description

Multi-targeted tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors represent two systemic modalities that has improved outcomes in patient with metastatic clear cell renal cell carcinoma (ccRCC). However, as an increasing number of treatment approaches has been sequentially approved in the front line setting, the optimal treatment selection and sequence have yet to be clearly defined. First line combination immunotherapy with nivolumab (PD-1 inhibitor) plus ipilimumab (CTLA-4 Inhibitor) has demonstrated improved overall survival and patient quality of life compared to Sunitinib in patients with IMDC intermediate and poor risk disease, but the primary progression rate of 20% poses a concern. Comparatively, a number of TKI plus CPI combinations have demonstrated even higher response rates and lower rates of primary progression, however the higher rate of significant adverse events and non-improvement in patient quality of life compared to Sunitinib are areas of concern. Cabozantinib, a potent, multiple-receptor TKI targeting MET, vascular endothelial growth factor receptor (VEGFR), AXL, and RET), is currently approved for the first and second line treatment of advanced RCC. Importantly, AXL and other targets such as TYRO3 and MER have been implicated in promoting tumor-immune suppression, and preclinical studies and clinical observations on circulating immune suppressive cells and immune effector cells suggest that Cabozantinib promotes an immune-permissive environment through inhibition of immune-modulatory targets on immune cells. This presents an opportunity for synergistic effects from combining CPI treatment with Cabozantinib. The researchers hypothesize that a sequential approach of Cabozantinib treatment course followed by immediate Ipilimumab plus Nivolumab may retain synergistic effects seen with concurrent therapy with an improved safety profile. Although anti-angiogenesis TKI therapy is effective both as monotherapy or in combination with ICI, continuous use can lead to persistent side effects, potentially compromising patient's quality of life. Thus, a rapid sequential treatment approach may optimize the therapeutic effect and preserve patient quality of life. The rapidly-cycling treatment regimen contains three, separate, consecutive treatment modules, each lasting 12 weeks: 1. Cabozantinib; 2. Ipilimumab + Nivolumab; 3. Nivolumab or Cabozantinib or Lenvatinib plus Everolimus depending on the response to the first and second modules. Primary objective is to evaluate the overall response rate after treatment with Cabozantinib and Ipilimumab plus Nivolumab. Additional exploratory objective are to evaluate the safety of this rapid sequencing treatment, as well as correlation of tissue and blood based biomarkers at various times-points with clinical outcome measures. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05188118
Study type Interventional
Source Icahn School of Medicine at Mount Sinai
Contact Che-Kai Tsao, MD
Phone 212-824-8782
Email che-kai.tsao@mssm.edu
Status Recruiting
Phase Early Phase 1
Start date February 24, 2023
Completion date December 2025

See also
  Status Clinical Trial Phase
Active, not recruiting NCT04987203 - Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Phase 3
Recruiting NCT06391879 - Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Terminated NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Withdrawn NCT05418387 - A Social Support Intervention to Improve Treatment Among Hispanic Kidney and Liver Cancer Patients in Arizona N/A
Recruiting NCT04623502 - An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy N/A
Completed NCT02853344 - Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427) Phase 2
Terminated NCT04088500 - A Study of Combination Nivolumab and Ipilimumab Retreatment in Patients With Advanced Renal Cell Carcinoma Phase 2
Completed NCT05070637 - Circulating Tumor Cell Reducing No-touch Nephrectomy N/A
Active, not recruiting NCT03634540 - A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003) Phase 2
Not yet recruiting NCT06049030 - A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Completed NCT01358721 - Phase I Biomarker Study (BMS-936558) Phase 1
Active, not recruiting NCT04503148 - Anesthesia and Cancer Study: Renal Cell Carcinoma N/A
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Not yet recruiting NCT05808608 - A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma Phase 1/Phase 2
Withdrawn NCT03323710 - Study of Propranolol Plus Sunitinib in First-line Treatment of Metastatic Renal Cell Carcinoma Phase 2
Completed NCT03052504 - Prospective Versus Retrospective Complications in Radical Cystectomy and Nephrectomy