PCSK9 Inhibitors in Combination With Advanced Treatment Strategies for the Treatment of Advanced Colorectal Cancer With pMMR/MSS

The purpose of this study is to preliminarily observe the efficacy and safety of PCSK9 inhibitors in combination with standard advanced first-line regimens in the treatment of advanced colorectal cancer with pMMR/MSS.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: standard advanced first-line regimen group; Drug: PCSK9 inhibitor in combination with standard advanced first-line regimen group

Detailed Description

The purpose of this study is to preliminarily observe the efficacy and safety of PCSK9 inhibitors in combination with standard advanced first-line regimens in the treatment of advanced colorectal cancer with pMMR/MSS. To evaluate progression-free survival (PFS) after PCSK9 inhibitor combination, overall survival (OS) after PCSK9 inhibitor combination, and to evaluate the safety and tolerability of PCSK9 inhibitor combination therapy based on NCI-CTCAE version 4.03, and to further explore efficacy predictive biomarkers based on changes in the expression of specific immune markers in blood and tissue specimens at baseline and after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YONG LI, Doctor; Phone Number: 13822177479; Email: liyong@gdph.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-75 years old, gender is not limited, and signed informed consent;
2. Histologically confirmed colorectal adenocarcinoma with pMMR/MSS;
3. Colorectal cancer with distant metastasis or inability to be radically surgically resected as assessed by imaging examination Patient;
4. Immunohistochemistry or sequencing to evaluate the high expression status of PCSK9 in tumors;
5. ECOG score 0-1;
6. Expected survival ≥ 3 months.

Exclusion Criteria:

1. Hypocholesterolemia, hypolipidemia and its family history, previous allergic reaction to PCSK9 inhibitors History of allergic reaction to PCSK9 inhibitors;
2. preoperative pathological diagnosis of advanced colorectal adenocarcinoma without pMMR/MSS, with the chance of radical surgical treatment;
3. Hypolipidemia caused by combination with other long-term lipid-lowering drugs;
4. malignancies other than colorectal cancer with negligible risk of metastasis or death (e.g., expected 5-year OS >90%) within 5 years prior to enrollment and for which a radical outcome is expected after treatment (e.g., adequately treated carcinoma in situ of the uterine cervix, basal or squamous cell skin cancers, limited prostate cancers treated for radical purposes, ductal carcinomas in situ treated for radical purposes surgically), with the exception of (b) the following;
5. history of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis;
6. major surgery within 4 weeks prior to enrollment or incomplete recovery from previous surgery;
7. systemic immunostimulatory drug therapy (including but not limited to interferon or IL-2) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to enrollment;
8. pre-existing or clinically significant CNS disease at screening, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndromes, or psychiatric disorders;
9. receipt of systemic corticosteroids (>10 mg/d prednisone equivalent) or other systemic immunosuppressants, etc. within 2 weeks prior to randomization;
10. previous allogeneic bone marrow transplantation or previous solid organ transplantation;
11. subjects who, in the judgment of the Investigator, have any factors affecting compliance with the protocol, including uncontrollable medical, psychological, familial, sociological, or geographic conditions; or who are unwilling or unable to comply with the procedures required in the study protocol;
12. history of idiopathic pulmonary fibrosis, drug-induced pneumonia, organic pneumonia (i.e., occlusive bronchiolitis), idiopathic pneumonia, or evidence of active pneumonia on CT scan of the chest at the time of screening; 13. receipt of any live vaccine (e.g., vaccines against infectious diseases such as influenza vaccine, varicella vaccine, etc.) within 4 weeks (28 days) prior to randomization

14. Pregnant or lactating female patients;

15. Hypersensitivity to fluorouracil-based or platinum-based agents or their excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Late standard first-line treatment regimen group; Fluorouracil and platinum were used as the basic chemotherapy regimens, with or without targeted therapy, and no additional injection of PCSK9 inhibitors	Drug: standard advanced first-line regimen group; Fluorouracil and platinum were used as the basic chemotherapy regimens, with or without targeted therapy, and no additional injection of PCSK9 inhibitors
Experimental: PCSK9 inhibitor in combination with standard advanced first-line regimen group; Fluorouracil and platinum as the base chemotherapy regimen, with or without targeted therapy, was administered subcutaneously at a fixed dose of 150 mg of PCSK9 inhibitor every two weeks starting on day 1 of patient enrollment	Drug: PCSK9 inhibitor in combination with standard advanced first-line regimen group; Fluorouracil and platinum as the base chemotherapy regimen, with or without targeted therapy, was administered subcutaneously at a fixed dose of 150 mg of PCSK9 inhibitor every two weeks starting on day 1 of patient enrollment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rateObjective response rate (ORR)	Objective response rate (ORR) after PCSK9 inhibitor in combination with standard advanced first-line regimen in patients with advanced colorectal cancer with pMMR/MSS	5years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) after PCSK9 inhibitor combination therapy	5years
Overall survival (OS)	Overall survival (OS) after PCSK9 inhibitor combination therapy	5years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation index	According to NCI-CTCAE version 4.03, the safety and tolerability of PCSK9 inhibitor combination therapy	During the study

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2024
• Primary Completion (Estimated): April 6, 2028
• Study Completion (Estimated): May 6, 2028

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: chemotherapy; PCSK9; pMMR/MSS
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Serine Proteinase Inhibitors; PCSK9 Inhibitors
• Other Study ID Numbers: lron-Man 02

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
• product manufactured in and exported from the U.S.: No