High- and Low-dose Radiotherapy Combined With PD-1 Inhibitors for MSS CRLM (HaRyPOT)

High- and Low-dose Radiotherapy Combined With PD-1 Inhibitors for Microsatellite Stable (MSS) Colorectal Liver Metastases (CRLM)

This pilot phase I trial aims to investigate the efficacy and safety of high- and low-dose radiotherapy combined with programmed cell death-1 (PD-1) inhibitors in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that have failed second-line immunotherapy or above.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Liver Metastases
• Intervention / Treatment: Radiation: Radiation: High- and Low-dose radiotherapy; Drug: PD-1 Inhibitors

Detailed Description

This pilot phase I trial aims to investigate the efficacy and safety of high- and low-dose radiotherapy combined with programmed cell death-1 (PD-1) inhibitors in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that have failed second-line immunotherapy or above. 30 participants will be enrolled in this study. All will take part at Jiangsu Cancer Hospital.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuxuan Ding; Phone Number: 18951590901; Email: dyxoo99@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Jiangsu Cancer Hospital
      • Contact: Yuxuan Ding; Phone Number: 18951590901; Email: dyxoo99@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with microsatellite stable colorectal liver metastases and failure with second-line or above therapy, and no subsequent standard treatment regimen.
2. Patients with an ECOG score of 0 or 1, and an expected survival period of ≥6 months.
3. During the study, they are willing to follow the arrangement and not use other systemic anti-tumor drugs such as chemotherapy, targeted, Chinese herbal medicine, and proprietary Chinese medicine.
4. 18-70 years old, no gender limit.

Exclusion Criteria:

1. Those with a history of severe immediate allergy to the drugs used in this study.
2. Cancer patients who require urgent surgical intervention, such as high-risk pathological fractures, life-threatening bleeding symptoms, etc.
3. Any of the following conditions in the 6 months before screening: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient cerebral ischemia Onset or symptomatic pulmonary embolism. Patients with known coronary artery disease, congestive heart failure that does not meet the above criteria or left ventricular ejection fraction <50% must adopt an optimized and stable medical plan determined by the treating doctor. If appropriate, you can consult a cardiologist.
4. Patients with active infection requiring systemic treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High- and Low-dose radiotherapy combined with immunotherapy.; All eligible patients will receive high-dose radiotherapy, followed by low-dose radiotherapy combined with PD-1 inhibitor therapy starting within 7 days after completion. The single dose of high-dose radiotherapy will be 6-8 Gy for 3-7 consecutive exposures, and the single dose of low-dose radiotherapy will be 0.5-1.4 Gy for 3-7 consecutive exposures.The PD-1 inhibitor (Zimberelimab) will be administered at the dose recommended in the specification every 3 weeks until disease progression, unacceptable toxicity, and withdrawal of informed consent by the patient.

Radiation: Radiation: High- and Low-dose radiotherapy; High-dose radiotherapy (6-8Gy×3-7F) followed by low-dose radiotherapy (0.5-1.4Gy×3-7F) starting within 7 days after completion.; Drug: PD-1 Inhibitors; Immunotherapy (Zimberelimab) is given every three weeks within one week after the end of high-dose radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The proportion of patients showing complete or partial response of low-dose radiotherapy lesions and other metastatic lesions assessed by RECIST v1.1	1,3,6, and 12 months after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	From the start of treatment to the date of progression or death	12 months
Overall survival (OS)	the time from the start of treatment to death from any cause	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation	NCI-CTCAE version 5.0 to assess adverse events (therapeutic toxicity)	12 months

Collaborators and Investigators

• Sponsor: Jiangsu Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 20, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: September 13, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: microsatellite stable; PD-1 Inhibitors; abscopal effects
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: HaRyPOT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No