Adebrelimab Plus Cetuximab and Chemotherapy for Patients With RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer

A Single-arm, Open-label, Phase Ⅱ Clinical Trial of Adebrelimab Plus Cetuximab and Chemotherapy for Patients With RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer

The purpose of this study is to observe and evaluate the efficacy and safety of adebrelimab plus cetuximab and chemotherapy for patients with RAS/BRAF wild-type unresectable liver metastases colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Adebrelimab + Cetuximab+ Chemotherapy

Detailed Description

Colorectal cancer is the third largest malignant tumor in the world and a significant cause of cancer-related deaths. The probability of simultaneous liver metastasis in colorectal cancer is about 25%, and the proportion of liver metastasis occurring in the entire disease process is as high as 40% -50%. It is of great clinical significance to transform the initial unresectable liver metastases of colorectal cancer into resectable ones to improve the overall survival rate and prognosis of colorectal cancer patients. We designed a single-arm, open phase II clinical trial of adebrelimab plus cetuximab and chemotherapy for patients with RAS/BRAF wild-type unresectable liver metastases colorectal cancer. The purpose of this study is to observe and evaluate the efficacy and safety of adebrelimab plus cetuximab and chemotherapy for patients with RAS/BRAF wild-type unresectable liver metastases colorectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hong Zong; Phone Number: 13523586882; Email: zonghong522@126.com

Study Locations

• China
  • Zhengzhou, China
    • Recruiting
    • The First Affiliated Hospital of Zhengzhou University
    • Contact: Hong Zong

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients who have fully understood and voluntarily signed informed consent forms for this study, have good compliance, and cooperate with follow-up; 2. Age ≥ 18 years and ≤ 75 years old; 3. ECOG 0-1; 4. Expected survival time ≥ 12 weeks; 5. Patients confirmed by histology or pathology to have colon or rectal glands; 6. Primary or metastatic tumors of the colon are identified as RAS/BRAF wild-type; 7. PET/CT scan, CT scan, MRI or intraoperative exploration diagnosis (if applicable during resection of primary colorectal tumor), record evidence of limited liver metastasis in the patient (histological confirmation of liver metastasis is not required); 8. Primary colorectal cancer can be or has been radically resected, initial inability to R0 resection of liver metastases, or residual liver volume ≤ 30-40% after resection; 9. The patient has at least one measurable liver metastasis lesion (according to RECIST 1.1 standard); 10. There was no previous liver metastasis chemotherapy; 11. The main organ function is normal, which meets the following criteria:

1. Blood routine examination criteria should be met (no blood transfusion and blood products within 14 days, no correction with G-CSF and other hematopoietic stimulating factors):

   A. Hemoglobin (Hb) ≥ 90 g/L; B. Neutrophil count (ANC) ≥ 1.5 × 109/L; C. Platelet count (PLT) ≥ 100 × 109/L;

2. Biochemical examination must meet the following standards:

   A. Total bilirubin (TBIL)<1.5 upper limit of normal value (ULN); B. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are less than 2.5 ULN, while for patients with liver metastasis, they are less than 5 ULN; C. Serum creatinine (Cr) ≤ 1.5 ULN or endogenous creatinine clearance rate>60ml/min (Cockcroft Gault formula); D. The urine routine test results show that urine protein (UPRO)<2+or 24-hour urine protein quantification<1g;

3. Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%);
4. Coagulation function: International standardized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time ≤ 1.5 × ULN;
5. Pulmonary function: First second forced expiratory volume (FEV1) ≥ 1.2 L, FEV1% ≥ 50%, carbon monoxide diffusion volume (DLCO) ≥ 50%;
6. Other: lipase ≤ 1.5 × ULN (if lipase>1.5) × ULN can be included if there is no clinical or imaging confirmation of pancreatitis; Amylase ≤ 1.5 × ULN (if amylase>1.5 × ULN can be included if there is no clinical or imaging confirmation of pancreatitis; Alkaline phosphatase (ALP) ≤ 2.5ULN.

12.Women of reproductive age should agree that effective contraception must be used during the study period and for 6 months after the study ends; Have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be a non-lactating patient; Men should consent to patients who must use contraception during the study period and for 6 months after the end of the study period;

Exclusion Criteria:

Patients who had any of the following symptoms were excluded from the study:

1. Individuals who are allergic to treatment drugs;
2. Patients who have received standard treatment for liver metastasis colorectal cancer;
3. Previously received anti-tumor therapy or radiation therapy for any malignant tumor;
4. Simultaneously receiving anti-tumor therapies in other clinical trials, including endocrine therapy, bisphosphate therapy, or immunotherapy;
5. Has undergone significant surgical procedures unrelated to colorectal cancer within 4 weeks prior to enrollment, or the patient has not fully recovered from such surgical procedures;
6. Patients with extrahepatic metastasis, unresectable lymph nodes (including portal vein lymph nodes) metastasis, and primary tumor recurrence;
7. Patients whose imaging shows that the tumor has invaded important blood vessels or who have been determined by the researchers to be highly likely to invade important blood vessels and cause fatal massive bleeding during subsequent studies
8. Within 5 years, subjects have had or co-developed other malignancies requiring active treatment
9. Existence of active autoimmune diseases or immunodeficiency, or a history of autoimmune hepatitis, interstitial pneumonia, uveitis, rheumatoid arthritis, inflammatory bowel disease, pituitary inflammation, vasculitis, nephritis, etc.
10. Individuals who test positive for HIV or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or allogeneic hematopoietic stem cell transplantation. The following exceptions apply: Patients with a history of autoimmune hypothyroidism who have received thyroid hormone replacement therapy may be included in the study. Patients with type 1 diabetes whose blood sugar can be controlled after treatment with insulin administration scheme can participate in this study.
11. The patient is currently using immunosuppressive agents or systemic hormone therapy to achieve immunosuppressive effects (dosage>10mg/day prednisone or other therapeutic hormones) and continues to use them within 2 weeks prior to enrollment;
12. Patients who have received systemic treatment with high-dose antibiotics within the past 2 weeks;
13. Individuals who have experienced arterial/venous thrombosis events within 6 months prior to the first administration, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral embolism, etc.), deep vein thrombosis, and pulmonary embolism;
14. Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting surgery within 6 months prior to enrollment; Congestive heart failure: New York Heart Association (NYHA) grade ≥ 2; Ventricular arrhythmia requiring medication treatment (including QTc interval ≥ 450 ms for males and ≥ 470 ms for females); Left ventricular ejection fraction (LVEF)<50%;
15. Active or uncontrolled severe infection (≥ CTCAE5.0 grade 2 infection), including but not limited to hospitalization due to infection complications, bacteremia, or severe pneumonia, unexplained fever>38.5 ℃ before the first administration;
16. Thoracic effusion, pericardial effusion, or ascites with clinical symptoms that require frequent drainage as determined by the researcher;
17. Cirrhosis and active hepatitis; Hepatitis B reference: HBsAg is positive, and HBV DNA exceeds the upper limit of normal value (1000 copies/ml or 500 IU/ml); Patients with past hepatitis B virus (HBV) infection or cured HBV infection (defined as the presence of hepatitis B B core antibody [HBcAb] and the absence of HBsAg, and the normal HBV DNA value detected during the screening period can be included; Hepatitis C reference: HCV antibody positive, and the detection value of HCV virus titer exceeds the upper limit of the normal value/HCV RNA or HCV Ab detection indicates acute and chronic infection;
18. Urine routine indicates urine protein ≥++, and it is confirmed that the 24-hour urine protein quantification is greater than 1.0 g;
19. Individuals with a history of psychiatric drug abuse who are unable to quit or have mental disorders;
20. Patients with pulmonary fibrosis, pneumoconiosis, radiation pneumonia, drug-induced pneumonia, and severe pulmonary dysfunction;
21. Pregnancy (positive pregnancy test before medication) or breastfeeding women;
22. Within 28 days prior to enrollment in this study, surgery (excluding biopsy) was performed or the surgical incision did not fully heal;
23. Received or planned to receive attenuated live vaccines within 4 weeks prior to the first administration;
24. Have received any other investigational drug treatment or participated in other intervention studies within 4 weeks prior to signing the informed consent form;
25. According to the researcher's judgment, patients who are deemed unsuitable for enrollment;

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: Adebrelimab + Cetuximab+ Chemotherapy	Drug: Adebrelimab + Cetuximab+ Chemotherapy; Adebrelimab:1200 mg, D1, Q2W+Cetuximab:500 mg, D1, Q2W+FOLFOX6(Q2W) or FOLFIRI(Q2W) until PD or resectability or to max 12 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The ration of patients who are evaluated as CR or PR	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Time form treament initation to the first disease progression or death from any cause	up to 2 years
Overall survival (OS)	Time from treatment initiation until death from any reason	up to 2 years
The R0 resection rates The R0 resection rates	The percentage of patients who had a curative (R0) liver metastasectomy following protocol treatment	1 year
Adverse events (Safety）	adverse events	up to 2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Estimated): January 19, 2025
• Study Completion (Estimated): January 19, 2026

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: January 21, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 21, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: S2023-K019-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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