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

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

NCT ID: NCT06076135

Condition: Metastatic Malignant Solid Neoplasm
Radiotherapy
Immune Checkpoint Blockade
Resistance to Immunotherapy

Conditions: Official terms:
Immune Checkpoint Inhibitors

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Intestinal Low Dose Radiotherapy-1Gy
Description: 1Gy ILDR will be administered to patients in a single fraction. The radiation treatment volume composes both the jejunum and ileum.
Arm group label: Treatment Stage Ⅰ

Intervention type: Radiation
Intervention name: Intestinal Low Dose Radiotherapy-2-3Gy
Description: 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.
Arm group label: Treatment Stage Ⅱ

Intervention type: Drug
Intervention name: PD-1/PD-L1 Inhibitors
Description: 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.
Arm group label: Treatment Stage Ⅰ
Arm group label: Treatment Stage Ⅱ

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Age ≥18 years, ≤80 years, regardless of gender. 2. ECOG level 0-2. 3. Expected life span>3 months. 4. At least one accessible and measurable lesion should be selected as the target lesion for observation according to RECIST criteria. 5. Patients with metastatic solid tumors (of any histology) without standard therapy options, who have previously received immunotherapy, immunotherapy combined with chemotherapy, or immunotherapy combined with anti-angiogenesis treatment and have shown disease progression. 6. The patient is considered ineligible for surgical treatment. 7. Patients with brain metastases assessed as clinically stable after treatment through repeated CT and/or MRI scans are eligible. 8. Patients have complete clinical and pathological information. 9. Any psychological, family, social or geographical conditions may hinder compliance with the research protocol. 10. Patients are able to understand the informed consent form, voluntarily participate, and sign the informed consent form. 11. Other indicators accord with the general inclusion criteria for clinical trials. Exclusion Criteria: 1. Patients with contraindications to radiation therapy and immunotherapy. 2. Previous occurrence of unacceptable immune related toxic side effects (immune myocarditis, pneumonia, etc.). 3. Patients who were assessed as hyperprogressive disease (HPD). 4. Patients who have received pelvic and abdominal radiation therapy within 6 months prior to enrollment. 5. The adverse reactions from prior treatment have not yet recovered to a CTCAE5.0 rating of ≤ 1 (excluding toxicity that has been determined to be risk-free, such as fatigue or hair loss). 6. Accompanied by severe infections. 7. Serious liver disease (such as cirrhosis), kidney disease, respiratory disease, or chronic system diseases such as uncontrollable diabetes and hypertension; Patients who cannot tolerate radiation therapy. 8. Clinical symptoms of brain metastases or meningeal metastasis. 9. The patients with known allergies or allergies to the test drug ingredients. 10. Substance/alcohol abuse. 11. Patients who are pregnant or planning to. 12. Patients participating in other clinical studies that may affect the efficacy/safety of this clinical study. 13. Patients who have undergone major surgical procedures within 30 days. 14. Patients who have received antibiotics, antifungal drugs, antiviral, antiparasitic drugs, or probiotics within 4 weeks.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Cancer Hospital, Shantou University Medical College

Address:
City: Shantou
Zip: 515031
Country: China

Status: Recruiting

Contact:
Last name: Chuangzhen Chen, MD

Phone: 86-13923995569
Email: stccz@139.com

Investigator:
Last name: Chuangzhen Chen, MD
Email: Principal Investigator

Start date: December 26, 2023

Completion date: September 30, 2026

Lead sponsor:
Agency: Chuangzhen Chen
Agency class: Other

Source: Shantou University Medical College

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06076135