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

Browse trials for

• Colorectal Neoplasms 5,599

Keywords

• colorectal cancer
• Hepatocyte nuclear factor 4α

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's planned enrollment of 9 is below the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Lead sponsor

Shanghai Changzheng Hospital is the lead sponsor of 125 studies on the registry; 60 are open to participants now.

Study arms

• Experimental
  HNF4α srRNA treatment

  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

• DrugHNF4α srRNA

  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.

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.

   Time frame: Through study completion, an average of 2 years

Secondary outcomes

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

   To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on RECIST v1.1. According to Amendment 1, the secondary endpoint has also been updated from evaluating the ORR per RECIST v1.1 with HNF4α srRNA therapy to evaluating the ORR for both monotherapy and combination therapy with HNF4α srRNA per RECIST v1.1.

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

2. Duration of response based on RECIST v1.1

   To assess the time from the first documentation of complete response or partial response to the date of first documentation of disease progression or death (whichever occurs first) based on RECIST v1.1

   Time frame: up to 24 months

3. Progression-free survival based on RECIST v1.1

   To assess the time from the first study dose date to the date of first documentation of disease progression or death(whichever occurs first) based on RECIST v1.1

   Time frame: up to 24 months

4. Time to response based on RECIST v1.1

   To assess the time from the date of first study dose to the date of first documentation of complete response or partial response based on RECIST v1.1

   Time frame: up to 24 months

5. Clinical benefit rate based on RECIST v1.1

   To assess the proportion of subjects who have best overall response of complete response or partial response or durable stable disease (duration of stable disease ≥ 23 weeks) based on RECIST v1.1

   Time frame: up to 24 months

6. Overall Survival

   To assess the time from the first study dose date until date of death from any cause . Subjects who are lost to follow-up and the subjects who are alive at the date of data cutoff will be censored at the date the subject was last known alive or the cut-off date, whichever comes earlier.

   Time frame: Throughout the entire course of treatment until the end of the follow-up period, an average of 2 years

7. Patient Reported Outcome-1

   the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The maximum and minimum values of the EORTC QLQ-C30 questionnaire depend on the specific items and domains. For items with 7 levels, the maximum value is 7 points, and the minimum value is 1 point; for items with 4 levels, the maximum value is 4 points, and the minimum value is 1 point. In the standardized scores, the theoretical maximum score is 100 points, and the minimum score is 0 points. However, under normal circumstances, a higher score does not always represent a better outcome, as the interpretation of the scores needs to be based on the specific items and domains of the scale.

   Time frame: Through study completion, an average of 2 years

8. Patient Reported Outcome-2

   Functional Assessment of Cancer Therapy Cololrectal Cancer (FACT-C). Each item has 5 levels, ranging from none to extreme. For assessments of functioning and overall health status, a higher score indeed indicates better patient conditions. However, for some symptom scales, such as pain or fatigue, a higher score actually signifies more severe issues.

   Time frame: Through study completion, an average of 2 years

9. Patient Reported Outcome-3

   The Generic Euroquol Five Dimension Five Level (EQ-5D-5L) Questionnaire. The EQ-5D-5L includes five dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression, each with 5 levels ranging from \'No problems\' to \'Unable to perform/Extremely severe\'. In addition, there is a Visual Analogue Scale (EQ VAS), which ranges from 0 (the worst health state you can imagine) to 100 (the best health state you can imagine). The EQ VAS score reflects an individual assessment of their overall health status. The scores of the EQ-5D-5L are not necessarily better when they are higher, as they reflect the individual health status relative to societal preferences.

   Time frame: Through study completion, an average of 2 years

10. The impact of HNF4α srRNA treatment on tumor biomarkers in serum

    The changes in tumor markers after treatment, including CA19-9, and carcinoembryonic antigen (CEA)

    Time frame: Through study completion, an average of 2 years

Other outcomes

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

   Identification of whether the efficacy of HNF4α srRNA is related to specific gene mutations in CRC tissue through next-generation sequencing

   Time frame: Through study completion, an average of 2 years

2. The impact of HNF4α srRNA treatment on cytokines in serum

   The detection of cytokines in patient serum before and after treatment of HNF4α srRNA

   Time frame: Through study completion, an average of 2 years

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

   The detection of immune cell subsets in patient serum or tissues before and after treatment of HNF4α srRNA

   Time frame: Through study completion, an average of 2 years