A Trial of Camrelizumab Combined With Microwave Ablation and Chemotherapy in the Treatment of Colorectal Cancer Liver Metastasis/Pulmonary Metastasis

Camrelizumab Combined With Microwave Ablation and Chemotherapy in the Treatment of Colorectal Cancer Liver Metastasis/Pulmonary Metastasis -a Single-arm Prospective Study

Currently, comprehensive treatments for liver metastasis/pulmonary metastasis that cannot reach NED include systemic chemotherapy, interventional chemotherapy, molecular targeted therapy, immunotherapy, and local treatments (ablation therapy, radiation therapy, etc.) for liver metastases. Combination therapy model of local ablation, systemic chemotherapy, and anti-PD -1 monoclonal antibody hopefully can prolong patient survival. This trial will evaluate the effectiveness and safety of carrelizumab combined with microwave ablation and chemotherapy in the treatment of colorectal cancer liver metastasis/pulmonary metastasis

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Metastases; Colorectal Cancer Metastatic; Liver Metastases
• Intervention / Treatment: Drug: Camrelizumab; Procedure: ablation; Drug: chemotherapy

Detailed Description

This is a phase II, single-arm prospective trial of local ablation combined with chemotherapy and camrelizumab for liver metastasis/pulmonary metastasis in colorectal cancer. The enrolled patients received ablation of liver metastases/pulmonary metastasis first, followed by chemotherapy (standard treatment plan for advanced colorectal cancer, determined by the investigator) and camrelizumab treatment (200mg, iv, q3w) one week later. If the patient has multiple metastatic tumors, ablation therapy needs to be performed in multiple times. Sequential chemotherapy and camrelizumab is administered one week after each ablation therapy. Treatment will continue until disease progression, unacceptable toxicity, or voluntary patient withdrawal.

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yanqiao Zhang, Ph D; Phone Number: 13845120210; Email: yanqiaozhang@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Two types of imaging or histology/cytology confirmed colorectal cancer patients with liver metastasis/lung metastasis ;
2. Must have CT or MRI examination for the past 3 months;
3. In addition to ablation lesions, there are measurable metastatic lesions (spiral CT scan ≥10mm, meet mRECIST 1.1 standard);
4. Expected survival time> 3 months;
5. Patients who have received at least one prior systemic treatment;
6. The damage caused by the subject receiving other treatments has been restored;
7. Known KRAS, NRAS, BRAF and HER2 gene status;
8. Age: 18 to 70 years old, no gender limit;
9. ECOG PS: 0-2 points;

10. The functions of vital organs meet the following requirements:

    1. .Absolute neutrophil count ≥1.5×109/L, platelet ≥100×109/L, hemoglobin

       ≥9g/dL;

    2. . Bilirubin ≤1.5 times ULN (can be included in patients drained by retrograde technique); ALT and AST

       ≤5 times ULN

    3. . Creatinine <120μmol/ L, or MDRD creatinine clearance rate> 60 mL/min
11. Women of childbearing age must have a negative pregnancy test (βHCG) before starting treatment, Women and men of childbearing age (have sex with women of childbearing age) must agree to use effective contraception during treatment and for 6 months after the last treatment dose is administered
12. Signature of patient information and informed consent

Exclusion Criteria:

1. Women who are pregnant or breastfeeding, or have fertility but refuse to take contraceptive measures;
2. Suffer from other malignant tumors within 5 years, except for fully treated cervical carcinoma in situ or skin squamous cell carcinoma, or skin basal cell carcinoma that has been basically controlled;
3. Those with uncontrolled, symptomatic brain metastases or a history of uncontrollable mental illness or severe intellectual or cognitive dysfunction;
4. Subjects with active, known or suspected autoimmune diseases, hypothyroidism requiring only hormone replacement therapy, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, or hair loss) Can be selected
5. Patients with active hepatitis B or C, chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) with a viral load of less than 500 IU/mL are allowed to participate in the study, but need to continue during the study period or start a full-course standardized antiviral treatment;
6. Congestive heart failure, uncontrollable arrhythmia, myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months; or other patients who cannot tolerate surgery;
7. Severe active infections that require intravenous antibiotic treatment occurred during the enrollment period;
8. Those who are allergic to test drugs;
9. Live vaccines have been vaccinated or will be vaccinated within 30 days before the administration of Camrelizumab;
10. Patients who cannot comply with the trial protocol or cannot cooperate with follow-up;
11. The researcher believes that it is inappropriate to participate in this trial.

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: Camrelizumab+ablation +chemotherapy; The enrolled patients received ablation of liver metastases/pulmonary metastasis first, followed by chemotherapy (standard treatment plan for advanced colorectal cancer, determined by the investigator) and camrelizumab treatment (200mg, iv, q3w) one week later. If the patient has multiple metastatic tumors, ablation therapy needs to be performed in multiple times. Sequential chemotherapy and camrelizumab is administered one week after each ablation therapy. Treatment will continue until disease progression, unacceptable toxicity, or voluntary patient withdrawal.

Drug: Camrelizumab; d1，200mg, iv, q3w; Procedure: ablation; the 37 enrolled patients received ablation of liver/lung metastases ，If the patient has multiple metastatic tumors, ablation therapy needs to be performed in multiple times.; Drug: chemotherapy; standard treatment plan for mCRC, determined by the investigator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month progression-free survival (PFS)	The date of first treatment until the date of progression using the RECIST 1.1 criteria, or death due to any cause,whichever comes first.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	ORR, which is defined as the proportion of subjects who achieve a best response of complete response(CR) or partial response (PR) using the RECIST 1.1 criteria.	3 years
Disease control rate (DCR)	DCR, which is defined as the proportion of subjects who achieve a response of complete response, partial response and stable disease (CR+PR+SD) in the total number of evaluable subjects using the RECIST 1.1 criteria.	3 years
progression-free survival (PFS)	The date of first treatment until the date of progression using the RECIST 1.1	3 years
Overall Survival(OS)	Overall Survival, defined from the date of first treatment to the date of death due to any cause.	3 years

Collaborators and Investigators

• Sponsor: Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Neoplasms, Second Primary
• Other Study ID Numbers: SHR-1210-HLJ-019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No