Neoadjuvant Immune-based Combinations in Patients Undergoing Nephrectomy for Locally Advanced ccRCC

Neoplasms Clinical Trial

Official title:

Phase II Trial of Neoadjuvant Immune-based Combinations in Patients Undergoing Nephrectomy for Locally Advanced ccRCC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06114940
• Other study ID #: 2022NZKY-002-01
• Status: Recruiting
• Phase: Phase 2
• Start date: December 20, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Jinling Hospital, China
• Contact: Le Qu, M.D.
• Phone: 15720625951
• Email: septsoul[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this single-center clinical trial was to evaluate the objective response rate and safety of Toripalimab combined with tyrosine kinase inhibitors TKI (Lenvatinib) in neoadjuvant treatment of（T2a-T4NanyM0 or TanyN1M0） clear cell renal cell carcinoma.

Description:

The objective of this single-center clinical trial was to evaluate the objective response rate and safety of Toripalimab combined with tyrosine kinase inhibitors TKI (Lenvatinib) in neoadjuvant treatment of（T2a-T4NanyM0 or TanyN1M0） clear cell renal cell carcinoma.Toripalimab is a new antibody that may help activate the immune system by blocking the function of the inhibitory molecule PD-1. This is a single-institution, single-arm Phase 2 clinical trial. Patients will be treated with Toripalimab in combination with tyrosine kinase inhibitors TKI (Lenvatinib) and patients will undergo partial or radical nephrectomy after neoadjuvant therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Imaging is consistent with(T2a-T4NanyM0 or TanyN1M0) clear cell renal cell carcinoma
• Puncture pathological biopsy was consistent with clear cell renal cell carcinoma
• Subjects were to undergo radical nephrectomy or partial nephrectomy or enucleation of renal tumor
• ECOG 0-1 points -Normal hematopoietic and organ function --
• Understand and plan visits, treatments, laboratory tests, and other research procedures.

Exclusion Criteria:

• Prior systemic anti-tumor treatment for RCC
• Patients who are receiving any other investigational agents.
• Clinical status indicating that immediate surgery (within 6 weeks) iswarranted regardless of whether neoadjuvant therapy is to beadministered, as assessed by the treating surgeon.
• Inability to undergo baseline tumor biopsy.
• Active or prior documented autoimmune or immunocompromisingconditions.
• Uncontrolled hypertension
• In the investigator's judgment, the subject has a medical history or current evidence of any disease, treatment, or laboratory abnormality that could confuse the results of the trial, interfere with the subject's participation throughout the trial, or is not in the subject's best interest to participate in the trial.

Related Conditions & MeSH terms

• Antineoplastic Agents
• Carcinoma
• Carcinoma, Renal Cell
• Female Urogenital Diseases
• Immune Checkpoint Inhibitors
• Kidney Diseases
• Kidney Neoplasms
• Male Urogenital Diseases
• Neoplasms
• Urogenital Diseases
• Urogenital Neoplasms
• Urologic Diseases
• Urologic Neoplasms

Intervention

Drug:
• Toripalimab
240mg, IV (in the vein) on on day 1 of 3-week, 6-week and 9-week for a total of 3 doses prior to partial nephrectomy or radical nephrectomy
• Lenvatinib
18 mg by mouth once each day for 12 weeks prior to nephrectomy

Locations

Country	Name	City	State
China	Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Jinling Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate of neoadjuvant treatment of (T2a-T4NanyM0 or TanyN1M0) clear cell renal cell carcinoma with Toripalimab combined with tyrosine kinase inhibitors TKI (Lenvatinib).	Tumor response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).	week 12 of neoadjuvant treatment
Secondary	Safety of neoadjuvant treatment of clear cell renal cell carcinoma with Toripalimab combined with tyrosine kinase inhibitors TKI (Lenvatinib).	Safety as assessed by number of participants experiencing adverse events.	up to 90 days after end of treatment
Secondary	Marginal negative (R0) rate of (T2a-T4NanyM0 or TanyN1M0)clear cell renal cell carcinoma treated with Toripalimab combined with TKI (Lenvatinib).	Marginal negative (R0) rate as assessed by number of participants experiencing Marginal negative (R0).	Baseline to date of surgery
Secondary	Disease-free survival (DFS) in(T2a-T4NanyM0 or TanyN1M0) clear cell renal cell carcinoma treated with Toripalimab combined with tyrosine kinase inhibitors TKI (Lenvatinib) neoadjuvant therapy.	DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.	Up to 5 years after surgery
Secondary	Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor	Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.	Baseline to date of surgery
Secondary	Change From Baseline in Regulatory T-cells (Tregs) in the Tumor	Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.	Baseline to date of surgery
Secondary	Change From Baseline in CD4+ T-cells in the Tumor	Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.	Baseline to date of surgery
Secondary	Change From Baseline in CD8+ T-cells in the Tumor	Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.	Baseline to date of surgery
Secondary	Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor	Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean ratio of Type 1 to Type 2 tumor associated macrophages using immunohistochemistry.	Baseline to date of surgery
Secondary	Change From Baseline of Selected Cytokines in Peripheral Blood	Cytokines measured in peripheral blood were soluble CD27 (sCD27), eotaxin, macrophage inflammatory protein 1b (MIP-1b), and soluble programmed cell death protein 1 (sPD-1).	Baseline to Day 43