NCT06076135

Intestinal Low Dose Radiotherapy Combined With Immunotherapy in Immune-resistant Metastatic Solid Tumors

Efficacy and Safety of Combining Intestinal Low Dose Radiotherapy and PD-1/PD-L1 Inhibitors for Metastatic Malignant Solid Tumors After Acquired Resistance to Anti-PD1/PD-L1 Treatment

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Chuangzhen Chen · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Preclinical and clinical studies have shown that intestinal low dose radiotherapy (ILDR) can enhance antitumor immunity and response to immune checkpoint blockade (ICB). Therefore, the investigators launch a phase Ⅱ trial to evaluate the clinical value of combining ILDR and programmed cell death-1/ -ligand 1 (PD-1/PD-L1) inhibitors in patients with ICB refractory metastatic solid tumor. This study is designed as a researcher-initiated, two-stage and prospective clinical trial. The target population is patients with advanced metastatic malignant solid tumors who have progressed after immunotherapy. The primary endpoints include objective response rate (ORR), disease control rate (DCR), progression free survival while receiving ILDR combined therapy (PFS2), and lesion-based abscopal response rate. The secondary endpoints include incidence of adverse events (AEs), cancer-specific survival (CSS), and overall response rate (OS). In the treatment stage Ⅰ, sixteen subjects will be enrolled in this trial. The primary objective of this stage is to evaluate the safety and efficacy of 1Gy ILDR combined with PD-1/PD-L1 inhibitors in immune-resistant metastatic malignant solid tumors, and biomarker exploration for response prediction. The inclusion criteria, exclusion criteria and sample size for treatment stage Ⅱ will be modified on the basis of results from Stage Ⅰ. The objective of the stage Ⅱ is to determine effects and safety of various dosage regimen of ILDR combined with PD-1/PD-L1 inhibitors in target patients. Eligible patients will be subjected to 1-3Gy ILDR. Tumor response will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as well as Immune related RECIST (iRECSIST). The extent or severity of adverse reactions will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0). Furthermore, tissue samples, stool samples, and peripheral blood samples will be collected for biomarker exploration.

Conditions

• Metastatic Malignant Solid Neoplasm
• Radiotherapy
• Immune Checkpoint Blockade
• Resistance to Immunotherapy

Interventions

Type	Name	Description
RADIATION	Intestinal Low Dose Radiotherapy-1Gy	1Gy ILDR will be administered to patients in a single fraction. The radiation treatment volume composes both the jejunum and ileum.
RADIATION	Intestinal Low Dose Radiotherapy-2-3Gy	ILDR will be administered as single fractions within 10 days. The total dose of radiotherapy will be 2-3 Gy in 2-3 fractions. ILDR design is as above.
DRUG	PD-1/PD-L1 Inhibitors	The immunotherapy regimen is the previous ICB therapy regimen or modified by the physician in charge. PD-1/PD-L1 inhibitors will be given 1 day after ILDR at a 3-week interval.

Timeline

• Start date: 2023-12-26
• Primary completion: 2025-09-30
• Completion: 2026-09-30
• First posted: 2023-10-10
• Last updated: 2025-06-15

Locations

1 site across 1 country: China