Real-world Study to Evaluate the Efficacy and Safety of Liposome Irinotecan

A Prospective, Multi-cohort, National Multicenter Real-world Study to Evaluate the Efficacy and Safety of Liposome Irinotecan

This study is a prospective, multicenter, real-world study. There are four cohorts. Cohorts 1-3 include second-line, posterior-line, and neoadjuvant colorectal cancer patients, respectively. Cohort 4 include patients with the exception of those with pancreatic and colorectal cancer. As this study is a real-world investigation, treatment procedures, visit schedules, and examinations will be based on the routine clinical practice of physicians. Through the above cohort, the efficacy and safety of irinotecan liposome are comprehensively observed.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Solid Tumor
• Intervention / Treatment: Drug: Irinotecan Liposome

• Study Type: Observational
• Enrollment (Estimated): 933

Contacts and Locations

• Study Contact: Name: Lin Shen; Phone Number: 01088196561; Email: doctorshenlin@sina.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Lin Shen, MD; Phone Number: (86)10-88196561; Email: shenlin@bjmu.edu.cn
      • Principal Investigator: Lin Shen, MD
      • Sub-Investigator: Jian Li, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This study was a prospective, multicenter real-world study with four cohorts. Cohort 1 include patients as second-line treatment for metastatic colorectal cancer. Cohort 2 include patients as a late-line treatment for metastatic colorectal cancer. Cohort 3 include patients as neoadjuvant chemotherapy for colorectal cancer.

Cohort 4 include patients as second-line or beyond treatment for nonpancreatic, noncolorectal cancers. Through the above cohort, the efficacy and safety of irinotecan liposome are comprehensively observed.

Description

Inclusion Criteria:

1. Cohort 1:

   • Patients with histologically or cytopathologically confirmed colorectal adenocarcinoma who were diagnosed with unresectable metastatic disease.
   • Known to be pMMR/MSS or MMR/MS status unknown.
   • Prior first-line systemic oxaliplatin - and fluorouracils-based therapy for metastatic disease progressed.
   • Patients had not received IRI or Nal-IRI during the treatment phase of metastatic disease.
   • Patients were scheduled to receive Nal-IRI plus fluorouracils or IRI plus fluorouracils chemotherapy regimens as second-line systemic therapy.

2. Cohort 2:

   • Patients with histologically or cytopathologically confirmed colorectal adenocarcinoma who were diagnosed with unresectable metastatic disease;
   • Known to be pMMR/MSS or MMR/MS status unknown.
   • Patients had received ≤ 3 lines of previous treatment for metastatic disease.
   • Progression of metastatic disease after treatment with an IRI-containing regimen (no limit on the number of IRI treatment lines).
   • The patient had not previously received Nal-IRI and was scheduled to receive a systemic Nal-IRI containing chemotherapy regimen as palliative treatment.
   • Have at least one measurable lesion according to RECIST v1.1.

3. Cohort 3:

   • High-risk (CRS score 3-5) synchronous liver metastatic colorectal adenocarcinoma with ≤5 liver metastases, confirmed by histopathology or cytopathology, and planned resection.
   • Known to be pMMR/MSS or MMR/MS status unknown.
   • The patient was scheduled to receive Nal-IRI+ oxaliplatin + fluorouracils chemotherapy regimen as neoadjuvant therapy.

4. Cohort 4:

   • Non pancreatic cancer and non colorectal cancer patients confirmed by histopathology and/or cytology.
   • Have received at least one systemic treatment for unresectable diseases;
   • Plan to receive a systemic treatment regimen containing Nal IRI;
   • At least one measurable lesion (according to RECIST v1.1);

Exclusion Criteria:

Cohort 1-4:

• Treatment with an immune checkpoint inhibitor (e.g., pembrolizumab, nivolumab) was planned during chemotherapy.
• Allergy to irinotecan or liposomal irinotecan and its excipients is known.
• Female patients known to be pregnant or lactating.
• Other patients who were deemed by the investigator to be ineligible for enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Second-line treatment for colorectal cancer; Cohort 1 is a concurrent control design, including patients treated with irinotecan liposome (Nal-IRI) or irinotecan (IRI) plus fluorouracils as second-line treatment for metastatic colorectal cancer.	Drug: Irinotecan Liposome; The experimental group will collect data from patients treated with Nal-IRI as the chemotherapy regimen. It is recommended to use according to the label, clinical practice shall prevail.
Posterior line treatment of colorectal cancer; Cohort 2 is a Simon two-stage design, is planned to include patients who are treated with a NAL-IRI based combination regimen and have used IRI as a late-line treatment for metastatic colorectal cancer.	Drug: Irinotecan Liposome; The experimental group will collect data from patients treated with Nal-IRI as the chemotherapy regimen. It is recommended to use according to the label, clinical practice shall prevail.
Neoadjuvant therapy for colorectal cancer; Cohort 3 is a single-arm design and planned to enroll patients who received Nal-IRI+ oxaliplatin + fluorouracils as neoadjuvant chemotherapy for colorectal cancer.	Drug: Irinotecan Liposome; The experimental group will collect data from patients treated with Nal-IRI as the chemotherapy regimen. It is recommended to use according to the label, clinical practice shall prevail.
Patients with non-pancreatic and non-colorectal cancer received second-line or above treatment; Cohort 4 is a single-arm design and is planned to enroll patients who are treated with the NAL-IRI containing regimen as second-line or beyond treatment for nonpancreatic, noncolorectal cancers.	Drug: Irinotecan Liposome; The experimental group will collect data from patients treated with Nal-IRI as the chemotherapy regimen. It is recommended to use according to the label, clinical practice shall prevail.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade ≥3 adverse events assessed by CTCAE 5.0 (Cohort 1)	To investigate the safety with Nal-IRI and IRI.	Assessed except to 10 months.
Objective response rate (Cohort 2 and 4)	To investigate antitumor efficacy of Nal-IRI, proportion of patients with complete (CR) or partial response (PR) assessed by RECIST v1.1.	From initial medication to the date of first documented progression or end of medication. Assessed up to 6 months.
R0 resection rate (Cohort 3)	To assess surgical conversion rates in patients who could be surgically resected.	From initial medication to the date of first documented progression or end of medication. Assessed up to 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (Cohort 1)	To investigate antitumor efficacy of Nal-IRI, proportion of patients with complete (CR) or partial response (PR) assessed by RECIST v1.1.	From initial medication to the date of first documented progression or end of medication. Assessed up to 6 months.
Disease control rate (Cohort 1,2,4)	To investigate antitumor efficacy of Nal-IRI, proportion of patients with complete , partial or stable response (SD) assessed by RECIST v1.1.	From initial medication to the date of first documented progression or end of medication.Assessed up to 6 months.
Progression free survival (Cohort 1,2,4)	To investigate antitumor efficacy of study. From initial medication to the date of first documented progression or end of medication, whichever came first.	From initial medication to the date of first documented progression or date of death from any cause, whichever came first. Assessed up to 24 months.
Overall survival (Cohort 1,2,4)	To investigate antitumor efficacy of Nal-IRI. From initial medication to the date of death from any cause.	From initial medication to the date of death from any cause. Assessed up to 42 months.
Incidence of adverse events and severity of adverse events as assessed by CTCAE 5.0 (Cohort 1,2,3,4)	To assess the incidence and severity of adverse events in combination regimens.	Assessed except to 24 months.
Pathological complete response rate (Cohort 3)	To investigate the effect of Nal-IRI.	After treatment and surgery, assessed up to 6 months.
Event-free survival (Cohort 3)	To investigate the effect of Nal-IRI.	The time from enrollment to any event, including death, disease progression, or switch to a treatment, occurred first. Assessed up to 12 months.

Collaborators and Investigators

• Sponsor: Peking University

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 5, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: June 4, 2024
• Last Verified: May 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: CSPC-DEY-CRC-K02

Drug and device information, study documents

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