A Phase II,Single-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab and Stereotactic Radiotherapy (SBRT) in Patients Advanced Metastatic Renal Clear Cell Carcinoma.

Nanfang Hospital, Southern Medical University2 sites in 1 country66 target enrollmentOctober 31, 2022

ConditionsClear-cell Metastatic Renal Cell Carcinoma

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Clear-cell Metastatic Renal Cell Carcinoma
Sponsor: Nanfang Hospital, Southern Medical University
Enrollment: 66
Locations: 2
Primary Endpoint: ORR
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This study is designed as a phase-II proof of clinical trial to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. Metastatic renal cell cancer (mRCC) patients with PD-1 expressing immune cells are more likely to have larger more aggressive tumours and reduced survival. Pembrolizumab is designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. SBRT will be given to the 1-5 most clinically significant lesions after the 1nd course of pembrolizumab treatment in an effort to improve the activity of pembrolizumab.

Registry

clinicaltrials.gov

Start Date

October 31, 2022

End Date

October 31, 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Nanfang Hospital, Southern Medical University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age\> 18 years at the time of signing informed consent;
•ECOG score of 0 or 1;
•Histologically confirmed, advanced ccRCC of stage IV (AJCC 8);
•Life expectancy of more than 12 weeks;
•Evidence of measurable metastatic kidney cancer according to RECIST 1.1 criteria. Patients should have an adequate number of non-irradiated metastatic sites in order to adequately assess the activity of the pembrolizumab therapy;
•If central nervous system (CNS) metastases are treated before inclusion and the patient's neurological system is present Return of symptoms to baseline levels (except for signs or symptoms associated with CNS therapy)At least 14 days, such patients may be included. In addition, patients must stop taking glucocorticoids or prednisone in a stable dose and ≤ 10 mg per day;
•Main organ function meets the following criteria within 7 days before treatment:
•blood examination criteria (in the state without blood transfusion within 14 days): ① Hemoglobin(HB) ≥ 70 g/L; ② Absolute Neutrophil Count(ANC) ≥ 1.0×109/L; ③ Platelet (PLT) ≥ 60×109/L.
•Biochemical examination shall meet the following criteria: ① total bilirubin within 1.5×the upper limit of normal(ULN); ② serum transaminase≤2.5×the Upper Limit of Normal(ULN), If associated with liver metastasis, serum transaminase≤5.0×the Upper Limit of Normal(ULN);③ serum creatine ≤ 1.5 x Upper Limit of Normal(ULN),creatinine clearance rate ≥ 60ml/min;
•Women of childbearing age should agree to use contraception (e. g. intrauterine device, contraceptive or condom) within 6 months after study completion, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative;

Exclusion Criteria

•Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2;
•Any active or recently diagnosed clear or suspected autoimmune disorder disease, or symptoms requiring glucocorticoids (\> 10 mg/day) or immunosuppressive drugs for systemic therapy;
•Active brain metastases and/or cancerous meningitis;
•Has had a prior monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier;
•Has more than one previous chemotherapy,targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent;
•Diagnosed with immunodeficiency within 2 weeks prior to study or being treated with systemic glucocorticoids or any other form of immunosuppressive therapy;
•Have a positive history of human immunodeficiency virus (HIV) test or have acquired immunodeficiency syndrome (AIDS);
•Has known active Hepatitis B or Hepatitis C;
•Has a known additional malignancy that is progressing or requires active treatment;
•Have interstitial lung disease, active pulmonary infectious pneumonia, or grade 3 or higher pneumonia;

Outcomes

Primary Outcomes

ORR

Time Frame: Approximately 2 months

Objective response rate by immune related response criteria (irRC), and RECIST 1.1 criteria

Secondary Outcomes

Overall survival(up to 24 months)
The disease control rate(up to 24 months)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(up to 24 months)