Liposomal Irinotecan and Leucovorin/5-fluorouracil Plus Bevacizumab in Metastatic Colorectal Cancer

October 7, 2024 updated by: Hebei Medical University Fourth Hospital

Liposomal Irinotecan + Leucovorin + 5-fluorouracil + Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer (IRIS)：a Multicenter, Single-arm, Prospective, Phase II Study

This is a multi-center, single-arm study to investigate the efficacy and safety of liposomal irinotecan+5-FU/LV+ bevacizumab as second-line therapy in metastatic colorectal cancer in Chinese population.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancer (CRC) has a poor prognosis and poses a serious threat to human health. FOLFIRI (irinotecan+5-FU/LV) / FOLFOX (oxaliplatin+5-FU/LV) ± angiogenesis inhibitors are common treatments for advanced CRC. For patients receiving oxaliplatin-based therapy, irinotecan-based therapy is recommended as second-line therapy. Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose, improve the efficacy and reduce the toxic side effects. The aim of this study is to explore the efficacy and safety of liposomal irinotecan+5-FU/LV + bevacizumab as second-line treatment for metastatic CRC.

Study Type

Interventional

Enrollment (Estimated)

173

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xuhua Hu, Doctor
  • Phone Number: 0311-86095347
  • Email: huxvhua@126.com

Study Locations

  • China
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Recruiting
        • The Fourth Hospital of Hebei Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: 18-75 years old.
  • Histologically or cytologically proven colon or rectum adenocarcinoma.
  • Confirmed as unresectable metastatic disease through radiological examination.
  • At least one measurable lesion (according to RECIST v1.1).
  • First-line treatment with oxaliplatin-based therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 2.
  • The expected survival time ≥3 months.
  • Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10^9/L.
  • Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present.
  • Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria <2+.
  • Normal coagulation function (INR≤1.5).
  • Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.

Exclusion Criteria:

  • Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
  • Previous treatment with irinotecan/liposomal irinotecan.
  • MSI-H/dMMR
  • Massive pleural effusion or ascites requiring intervention.
  • Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
  • Active HIV, HBV, HCV infection.
  • Combined with uncontrollable systemic diseases.
  • Presence of severe gastrointestinal disease (including active bleeding, > grade 1 obstruction , > grade 1 diarrhea or gastrointestinal perforation)
  • History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment.
  • Presence of interstitial pneumonia or pulmonary fibrosis.
  • Allergy to or intolerance to therapeutic drugs or their excipients;.
  • History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment.
  • Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment.
  • Patients with symptomatic central nervous system metastases.
  • Documented serum albumin ≤3 g/dL
  • Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
  • Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
  • Participated in other trial within 30 days prior to the first dose of study treatment.
  • Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug
  • Patients who are not suitable to participate in this trial for any reason judged by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Group
liposomal irinotecan+5-FU/LV+ bevacizumab q2w
Drug: liposomal irinotecan
liposomal irinotecan 70 mg/m²
Other Names:
  • nal-IRI
Drug: 5-FU
5-FU 2400 mg/m²
Other Names:
  • Fluorouracil
Drug: LV
5-FU 2400 mg/m²
Other Names:
  • Calcium folinate
Drug: Bevacizumab
bevacizumab 5 mg/kg
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: 4 months
Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate
Time Frame: 4 months
Defined as the percentage of patients who achieved CR, PR, and stable disease (SD) according to RECIST v1.1.
4 months
Duration of Response
Time Frame: 4 months
Defined as the time from the initiation of a response (first confirmation of CR or PR) to disease progression or death from any cause, whichever occurred first.
4 months
Progress-free survival
Time Frame: 6 months
Defined as time from the subject's enrollment to first documented disease progression using RECIST version 1.1 by investigator review or death due to any cause, whichever occurred first.
6 months
Overall survival
Time Frame: 1 year
Defined as the time between signing the informed consent form and death due to various causes.
1 year
Incidence of adverse events
Time Frame: 5 months
Use NCI-CTCAE version 5.0 for classification and grading
5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hebei Medical University Fourth Hospital

Investigators

  • Principal Investigator: Guiying Wang, Professor, Hebei Medical University Fourth Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

December 12, 2023

First Submitted That Met QC Criteria

December 24, 2023

First Posted (Actual)

December 28, 2023

Study Record Updates

Last Update Posted (Estimated)

October 9, 2024

Last Update Submitted That Met QC Criteria

October 7, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSPC-DEY-CRC-K04

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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