SABR Combined With Axitinib and Toripalimab for Oligometastatic Renal Cell Carcinoma

Official title

A Prospective, Single-Center, Single-Arm, Phase II Clinical Study of Stereotactic Ablative Radiotherapy Combined With Axitinib and Toripalimab in the Treatment of Oligometastatic Clear Cell Renal Cell Carcinoma

Overview

This is a phase II clinical trial testing whether a combination of stereotactic ablative radiotherapy (SABR), axitinib, and toripalimab is effective and safe for treating oligometastatic clear cell renal cell carcinoma (a type of kidney cancer that has spread to 5 or fewer sites). In this study, all metastatic tumors will be treated with SABR - a precise, high-dose radiation therapy delivered in 5 sessions. At the same time, participants will receive axitinib (an oral targeted cancer drug) twice daily, and toripalimab (an intravenous immunotherapy) every 3 weeks for up to 2 years. The study will enroll 48 participants. The main goal is to measure the objective response rate - the proportion of patients whose tumors shrink or disappear after treatment. Researchers will also track how long patients live without their cancer worsening, overall survival, and any side effects from the treatment. Participants will have regular imaging scans, blood tests, and quality-of-life assessments throughout the treatment and follow-up period.

Interventions

• Drug axitinib plus toripalimab
  Axitinib 5 mg administered orally twice daily continuously, combined with toripalimab 240 mg administered intravenously every 3 weeks for up to 35 cycles (approximately 2 years).
• Radiation SABR
  All participants receive stereotactic ablative radiotherapy (SABR) to all measurable metastatic lesions, delivering ≥7 Gy per fraction in 5 fractions, achieving a biologically equivalent dose (BED₃) ≥ 115 Gy based on α/β = 3 Gy. For lesions adjacent to organs at risk, partial-SABR is permitted. If SABR or partial-SABR is infeasible, moderately hypofractionated radiotherapy (MHFRT) with curative intent may be substituted at the discretion of the radiation oncologist.

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: From enrollment to the end of treatment (up to approximately 2 years)]

Secondary outcome measures (5)

• Local Control Rate [Time frame: From enrollment to the end of treatment (up to approximately 2 years)]
• Disease Control Rate (DCR) [Time frame: From enrollment to the end of treatment (up to approximately 2 years)]
• Progression-Free Survival (PFS) [Time frame: From first SABR to disease progression or death, whichever occurs first (up to approximately 4 years)]
• Overall Survival (OS) [Time frame: From first SABR to death from any cause (up to approximately 4 years)]
• Safety (Adverse Events) [Time frame: From first dose of study treatment to 30 days after last dose (up to approximately 2.5 years)]

Eligibility criteria

Inclusion criteria

Histologically confirmed diagnosis of clear cell renal cell carcinoma (ccRCC).

Age ≥ 18 years.

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Radiological evidence of distant metastasis meeting the MD Anderson (MDA) definition of oligometastatic disease: ≤5 metastatic lesions, all amenable to curative-intent local therapy. Lesions must be measurable per RECIST 1.1 criteria.

Prior definitive local therapy to the primary tumor, including surgery, stereotactic radiotherapy, or ablation.

Either no prior systemic therapy for metastatic disease (first-line naïve), or prior first-line tyrosine kinase inhibitor (TKI) therapy only with subsequent oligoprogression (≤5 progressive lesions with remaining lesions stable).

Adequate organ function:

Hemoglobin (Hb) ≥ 80 g/L

Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L

Platelet count (PLT) ≥ 75 × 10⁹/L

Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN

Voluntary written informed consent obtained, with commitment to complete all treatment and follow-up visits.

Exclusion criteria

Target lesions previously treated with radiotherapy with a biologically effective dose (BED₃) ≥ 60 Gy (calculated with α/β = 3 Gy).

Target lesions deemed unsuitable for radiotherapy by the treating radiation oncologist (e.g., lesions invading the gastrointestinal tract or penetrating the bronchus).

Uncontrolled malignant pleural effusion or ascites.

Presence of other uncured malignancies.

History of severe psychiatric illness interfering with understanding of informed consent or compliance with study procedures.

Severe cardiovascular disease: New York Heart Association (NYHA) class III-IV heart failure, uncontrolled arrhythmia, or myocardial infarction within the past 6 months.

Any other serious medical condition that, in the investigator's judgment, may pose significant risk or interfere with radiotherapy.

Pregnancy, breastfeeding, or planned pregnancy during the study period.

Any other reason determined by the investigator that makes the participant unsuitable for study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the Fourth Hospital of Hebei Medical University — Shijiazhuang

Identifiers

NCT: NCT07744932 · 2026KY221-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗