NCT07175480

PET/CT-Directed Free of Therapy for Metastatic RCC Patients With IMDC Favorable or Intermediate Risk

An Open-label, Investigator-initiated, Single Arm, Exploratory Phase 2 Trial Evaluating the Feasibility and Efficiency of PET/CT Directed Free of Therapy Used for Metastatic and Advanced Renal Cell Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Jinling Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase 2 trial aims to test the feasibility and efficiency of PET/CT-directed treatment interruption strategy in metastatic renal cell carcinoma patients with IMDC favorable/intermediate risk who achieve complete (CMR) or partial metabolic response (PMR) after ≥12 months of first-line PD-1/PD-L1 Immune checkpoint inhibitor (ICI)+ VEGFR-tyrosine kinase inhibitor (TKI) therapy. It helps figure out whether PET/CT can safely direct treatment pause as well as explores a new individualized treatment option based on metabolic imaging for RCC patients.

Detailed description

Current first-line therapy for advanced renal cell carcinoma (RCC) combines tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICIs). Although effective, continuous treatment often results in cumulative toxicities, significant financial burdens, and potential overtreatment for patients. To improve such limitations, intermittent therapy strategies has gained more attention. However, existing approaches are constrained by insufficient induction periods (\<12 months) that may compromise treatment depth, and reliance on anatomic CT criteria (RECIST 1.1) which cannot reliably differentiate residual active tumor from treatment-related fibrosis/necrosis. PET/CT quantifies tumor metabolic activity via standardized uptake values (SUV), enabling early molecular-level response assessment per PERCIST 1.0 criteria, thus shows promising prospects. This trial implements a two-stage screening approach. During the pre-screening period, eligible unresectable/metastatic RCC patients with IMDC low/intermediate risk sign the Pre-screening Consent Form to receive ≥12 months of standard ICI+TKI therapy. Consolidative surgery and consolidative radiotherapy during combination therapy are permitted. Patients achieving complete metabolic response (CMR) or partial metabolic response (PMR) on PET/CT within 24 months undergo main screening. Those qualifying sign the Informed Consent Form (ICF), discontinue both agents and enter a closely monitored treatment holiday. During this phase, serial imaging (CT with supplemental PET/CT when indicated) will be performed every 12 ± 1 weeks. Therapy will be restarted immediately if any of the following occur: * A ≥10% increase in the sum of the longest diameters (SLD) of target lesions from nadir, concurrent with a ≥30% increase in the peak standardized uptake value normalized to lean body mass (SULpeak) relative to baseline; * New lesion with SULpeak exceeding liver background. Peripheral blood and other biological samples from participants at different time points during the trial will be collected for future analyses. The primary endpoint is progression-free survival (PFS) rate at 24 months from treatment initiation. Secondary endpoints include duration of response after interruption, objective response rate after restarting therapy, safety (CTCAE v5.0-graded adverse events), patient-reported outcomes and cost-effectiveness. This study pioneers metabolic imaging to guide intermittent therapy in mRCC patients, utilizing extended induction and dual anatomic/metabolic restart thresholds to optimize risk-benefit balance while reducing treatment burden.

Conditions

• Renal Cell Carcinoma (RCC)
• Metastatic Renal Cell Carcinoma (mRCC)

Interventions

Type	Name	Description
DRUG	Intermittent PD-1/PD-L1 ICI + VEGFR-TKI	Any PD-1/PD-L1 inhibitor or VEGFR-TKI that is commercially marketed, regulatory-approved and reimbursed under public health plans.Dose as recommended by the manufacturer.

Timeline

• Start date: 2025-01-24
• Primary completion: 2027-08-01
• Completion: 2030-08-01
• First posted: 2025-09-16
• Last updated: 2025-09-16

Locations

1 site across 1 country: China