A Clinical Trial Evaluating the Safety and Efficacy of Intravenous HNF4α SrRNA in Treating Metastatic CRC Patients

NCT06621173 | Recruiting Early Phase 1

• 1 other identifier: CZXH-CRC-2024-IIT
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a single-arm, open-label, exploratory first-in-human clinical study designed to evaluate the safety and tolerability of HNF4α srRNA injection in patients with locally unresectable or metastatic colorectal cancer, and to preliminarily explore its effectiveness in treating metastatic colorectal cancer.

Conditions

Metastatic Colorectal Cancer (mCRC)

Keywords

colorectal cancer; Hepatocyte nuclear factor 4α

Outcome Measures

Primary Outcomes (1)

• To evaluate the tolerability and safety for intravenous HNF4α srRNA in subjects with metastatic colorectal cancer

  Safety and tolerability are assessed based on the incidence of Dose-Limiting Toxicities (DLTs) within 14 days post-initial drug administration, along with the frequency and severity of adverse events (AEs), serious adverse events (SAEs), and events leading to treatment discontinuation throughout the treatment period, all evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. According to Amendment 1, the primary endpoint has been amended from assessing the incidence and severity of DLTs, adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation (evaluated per NCI-CTCAE 5.0) with HNF4α srRNA therapy to assessing these outcomes for both HNF4α srRNA monotherapy and combination therapy.

  Through study completion, an average of 2 years

Secondary Outcomes (10)

• To assess the objective response rate (ORR) by RECIST v1.1

  From the first study dose date until the date of documented complete response or partial response, assessed up to 24 months.

• Duration of response based on RECIST v1.1

  up to 24 months

• Progression-free survival based on RECIST v1.1

  up to 24 months

• Time to response based on RECIST v1.1

  up to 24 months

• Clinical benefit rate based on RECIST v1.1

  up to 24 months

Other Outcomes (3)

• The assessment of whether the efficacy of HNF4α srRNA is related to specific mutations

  Through study completion, an average of 2 years

• The impact of HNF4α srRNA treatment on cytokines in serum

  Through study completion, an average of 2 years

• The impact of HNF4α srRNA treatment on immune cell subsets in serum or tissuses

  Through study completion, an average of 2 years

Study Arms (1)

HNF4α srRNA treatment

EXPERIMENTAL

The subjects with metastatic colorectal cancer will be treated by HNF4α srRNA intravenously via a peripheral vein. According to Amendment 1, the HNF4α srRNA preparation CD-801 used in the original protocol will expire on December 31, 2024. For participants receiving treatment after this date, the preparation will be switched to CD-GA-102, with the treatment dose converted on a 1:1 basis.

Drug: HNF4α srRNA

Interventions

HNF4α srRNA DRUG

HNF4α srRNA will be administered intravenously for the treatment of metastatic colorectal cancer. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. According to Amendment 1, after enrollment, the investigator will determine the HNF4α srRNA dose, whether to combine it with immunotherapy, and the dose and schedule of the combination, based on the patient's treatment history and the safety/efficacy data of HNF4α srRNA administered via peripheral vein for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or colorectal cancer. Participants initially on HNF4α srRNA monotherapy who are considered for combination with immunotherapy must complete at least two treatment cycles and the post - treatment safety assessment.

HNF4α srRNA treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, aged 18 years or older.
• Patients with histologically confirmed colorectal cancer that has been determined to be unresectable or metastatic.
• Colorectal cancer subjects who are unsuitable or unable to tolerate standard systemic therapy, or who have received standard systemic therapy but have disease progression based on RECIST (version 1.1) criteria, including chemotherapy based on fluorouracil, oxaliplatin, or irinotecan, and targeted therapies with anti-VEGF/EGFR monoclonal antibodies.
• Patients with confirmed deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) in tumor tissue, who have been treated with immune checkpoint inhibitors (anti-PD-1 or anti-PD-L1 antibodies) and are assessed with disease progression.
• According to the RECIST (version 1.1) criteria, there are measurable target lesions suitable for repeated measurements for assessment.
• Life expectancy of 12 weeks or more.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
• Males with fertility and females of childbearing potential are willing to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation. Females of childbearing age, including premenopausal females and within 2 years after menopause, must have a negative serum pregnancy test result within 7 days prior to the first dose of study treatment.
• Subjects who had a voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

You may not qualify if:

• Patients with any of the following criteria were excluded from participation in this study
• Patients who have undergone standard adjuvant chemotherapy after tumor resection, and have experienced recurrence or metastasis within 6 months after discontinuing the medication, and have not received standard systemic therapy.
• Clinical or imaging indications suggest the current presence of intestinal obstruction, perforation, or bleeding; or those who, upon investigator assessment, are at a higher risk of perforation or bleeding.
• Inadequate liver function：serum bilirubin \> 3 × the upper limit of normal (ULN), or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) \> 5 × ULN.
• Inadequate renal function defined as creatinine \>1.5 × ULN or calculated creatinine clearance \< 40 mL/min.
• Absolute neutrophil count (ANC) \< 1.5×109/L, or Platelets \< 50×109/L, or Hemoglobin \< 9.0 g/dL.
• International normalized ratio (INR) \> 2.0.
• Patients with confirmed tumor brain metastases.
• Poorly controlled hypertension, diabetes or other serious heart or lung diseases, or with serious dysfunction.
• Patients who have received local or systemic anti-tumor treatments such as immunotherapy, targeted therapy, and chemotherapy within 4 weeks, or radiation therapy within 3 weeks, except for treatment regimens assessed as disease progression according to RECIST v1.1.
• All toxicities related to prior locoregional or systemic anti-tumor treatments are still grade 2 or more (except for hair loss and other events that have been judged tolerable by researchers).
• Uncontrolled active infection (eg, lung infections, or abdominal infections).
• History of malignancy other than CRC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate \> 90%), such as adequately treated early gastric carcinoma, carcinoma in situ of the cervix, non-melanoma skin carcinoma, or localized prostate cancer.
• Having an active autoimmune disease that requires systemic treatment within the past 2 years.
• Any condition requiring systemic treatment with corticosteroids (prednisone or equivalent \>10mg/day) or other immunosuppressive drugs within 14 days prior to the first administration of the investigational drug.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Study Sites (1)

Shanghai Changzheng Hospital，Naval Medical University

Shanghai, Shanghai Municipality, 200003, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Wei-Fen Xie, MD. PhD

  Naval Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Beifang Ning, MD. PhD

CONTACT

13764001892; ningbeifang@163.com

Weifen Xie, MD. PhD

CONTACT

13701682806; weifenxie@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Gastroenterology, Changzheng Hospital

Model Details: The subjects with metastatic colorectal cancer will be treated by HNF4α srRNA intravenously via a peripheral vein.

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: October 1, 2024
• Study Start: November 12, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

CN (1)