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

Primary Purpose

Colorectal Liver Metastases

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Radiation: High- and Low-dose radiotherapy
PD-1 Inhibitors
Sponsored by
Jiangsu Cancer Institute & Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Liver Metastases focused on measuring microsatellite stable, PD-1 Inhibitors, abscopal effects

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with microsatellite stable colorectal liver metastases and failure with second-line or above therapy, and no subsequent standard treatment regimen. Patients with an ECOG score of 0 or 1, and an expected survival period of ≥6 months. 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. 18-70 years old, no gender limit. Exclusion Criteria: Those with a history of severe immediate allergy to the drugs used in this study. Cancer patients who require urgent surgical intervention, such as high-risk pathological fractures, life-threatening bleeding symptoms, etc. 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. Patients with active infection requiring systemic treatment.

Sites / Locations

  • Jiangsu Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

High- and Low-dose radiotherapy combined with immunotherapy.

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Progression-free survival (PFS)
From the start of treatment to the date of progression or death
Overall survival (OS)
the time from the start of treatment to death from any cause

Full Information

First Posted
September 13, 2023
Last Updated
September 13, 2023
Sponsor
Jiangsu Cancer Institute & Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06045286
Brief Title
High- and Low-dose Radiotherapy Combined With PD-1 Inhibitors for MSS CRLM
Acronym
HaRyPOT
Official Title
High- and Low-dose Radiotherapy Combined With PD-1 Inhibitors for Microsatellite Stable (MSS) Colorectal Liver Metastases (CRLM)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 20, 2023 (Anticipated)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jiangsu Cancer Institute & Hospital

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Liver Metastases
Keywords
microsatellite stable, PD-1 Inhibitors, abscopal effects

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High- and Low-dose radiotherapy combined with immunotherapy.
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radiation: High- and Low-dose radiotherapy
Intervention Description
High-dose radiotherapy (6-8Gy×3-7F) followed by low-dose radiotherapy (0.5-1.4Gy×3-7F) starting within 7 days after completion.
Intervention Type
Drug
Intervention Name(s)
PD-1 Inhibitors
Intervention Description
Immunotherapy (Zimberelimab) is given every three weeks within one week after the end of high-dose radiotherapy.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
The proportion of patients showing complete or partial response of low-dose radiotherapy lesions and other metastatic lesions assessed by RECIST v1.1
Time Frame
1,3,6, and 12 months after completion of radiotherapy
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
From the start of treatment to the date of progression or death
Time Frame
12 months
Title
Overall survival (OS)
Description
the time from the start of treatment to death from any cause
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Safety evaluation
Description
NCI-CTCAE version 5.0 to assess adverse events (therapeutic toxicity)
Time Frame
12 months

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with microsatellite stable colorectal liver metastases and failure with second-line or above therapy, and no subsequent standard treatment regimen. Patients with an ECOG score of 0 or 1, and an expected survival period of ≥6 months. 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. 18-70 years old, no gender limit. Exclusion Criteria: Those with a history of severe immediate allergy to the drugs used in this study. Cancer patients who require urgent surgical intervention, such as high-risk pathological fractures, life-threatening bleeding symptoms, etc. 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. Patients with active infection requiring systemic treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuxuan Ding
Phone
18951590901
Email
dyxoo99@163.com
Facility Information:
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuxuan Ding
Phone
18951590901
Email
dyxoo99@163.com

12. IPD Sharing Statement

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

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