Dose Escalation and Expansion Clinical Trial of Irinotecan Liposome Combined With Oxaliplatin and 5-FU/LV Plus Bevacizumab as First-line Treatment of Metastatic Colorectal Cancer

March 17, 2024 updated by: Tianshu Liu, Shanghai Zhongshan Hospital

Dose escalation clinical trial: To explore the dose limiting toxicity (DLT) of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab in first-line treatment of patients with advanced metastatic colorectal cancer, and to estimate the maximum tolerated dose (MTD) of combined administration.

Expansion clinical trial: To evaluate the safety and efficacy of irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab in first-line treatment of patients with advanced metastatic colorectal cancer. Exploratory analysis of ctDNA changes and genetic mutations in patients at baseline.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a dose escalation and expansion study to evaluate the safety and efficacy of irinotecan liposome injection in patients with first-line treatment for metastatic colorectal cancer. In the dose escalation phase, patients will be treated with a combination regimen of irinotecan liposome injection at doses of 60mg/m2, 70mg/m2, and 80mg/m2, and 9 to 18 eligible patients are expected to be enrolled. In the expansion phase, approximately 60 patients will receive combination therapy with irinotecan liposome RP2D dose and exploratory analysis of genetic mutations at baseline and ctDNA changes during treatment.

Study Type

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 1

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

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Zhongshan Hospital affiliated to Fudan University
        • Contact:
          • Tianshu Liu, Doctor

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:

  • 18-75 years old.
  • Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma.
  • The unresectable stage of metastatic disease has not received any systemic antitumor therapy.
  • For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 12 months removed from the date of last administration of neoadjuvant or adjuvant therapy.
  • The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria.
  • ECOG 0
  • Normal bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×10^9/L, platelets (PLT) ≥100×10^9/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×10^9/L, albumin (ALB) ≥35 g/L, and no bleeding tendency; ② AST, ALT and alkaline phosphatase (ALP) were all ≤2.5× upper limit of normal range (ULN), and ≤5×ULN when liver metastases occurred; The total bilirubin level doesn't exceed the upper limit of the agency's normal range; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated according to Cockroft-Gault)
  • Understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form.

Exclusion Criteria:

  • Patients with known MSI-H or dMMR who were evaluated by investigators as suitable for treatment with immune checkpoint inhibitors.
  • Patients allergic to the investigational drug and its excipients.
  • Underweight (body mass index [BMI]<18.5 kg/m^2).
  • Known or suspected central nervous system metastasis.
  • Received irinotecan before enrollment.
  • Had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment.
  • Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 class I or below.
  • The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment.
  • Serious gastrointestinal disorders.
  • Interstitial lung disease.
  • Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding).
  • Patients with fluid accumulation that couldn't reach a stable state and small amount of pleural effusion or ascites on imaging without clinical symptoms could be enrolled.
  • Intestinal obstruction, signs and symptoms of intestinal obstruction, or the stent has been previously implanted and the stent has not been removed before the screening period.
  • Gastrointestinal perforation, intraperitoneal abscess, and fistula.
  • Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc.
  • Have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer.
  • Patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding.
  • The researchers didn't consider it appropriate to participate in this study.

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: irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab
In dose escalation study, patients will be treated with irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab. In expansion study, patients will be treated with irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab, depending on their baseline mutation status. Oxaliplatin is accepted up to 12 cycles.
Drug: Irinotecan Liposome

In dose escalation study, irinotecan liposome injection will be administered by an intravenous infusion at three doses of 60 mg/m2, 70 mg/m2 and 80 mg/m2, d1, 14 days per cycle. In expansion study, irinotecan liposome injection will be administered by an intravenous infusion at the dose of RP2D, d1, 14 days per cycle.

Until the disease progresses or surgery is possible.

Drug: Oxaliplatin
85 mg/m2, intravenously infusion, d1, 14 days per cycle, up to 12 cycles.
Drug: 5-FU
2400mg/m2, intravenous infusion, d1-2, 14 days per cycle. Until the disease progresses or surgery is possible.
Drug: LV
400mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.
Drug: Bevacizumab
5mg/kg, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.It is used to patients in dose escalation phase and with gene mutation in extension phase.
Drug: Cetuximab
500mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.For wild-type patients in extended phase studies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose
Time Frame: Up to 14 days
To investigate the safety.
Up to 14 days
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: Start by signing the informed consent form until 4 weeks after the last dose.
To evaluate the incidence and severity of hematological adverse events in patients.
Start by signing the informed consent form until 4 weeks after the last dose.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: From initial medication to the date of first documented progression or end of medication, assessed up to 20 months.
To investigate the preliminary antitumor efficacy of study.
From initial medication to the date of first documented progression or end of medication, assessed up to 20 months.
Disease control rate
Time Frame: From initial medication to the date of first documented progression or end of medication , assessed up to 20 months.
To investigate the preliminary antitumor efficacy of study.
From initial medication to the date of first documented progression or end of medication , assessed up to 20 months.
Progression free survival
Time Frame: From initial medication to the date of first documented progression or date of death from any cause, whichever came first , assessed up to 22 months.
To investigate the preliminary antitumor efficacy of study.
From initial medication to the date of first documented progression or date of death from any cause, whichever came first , assessed up to 22 months.
R0 resection
Time Frame: From the first dose to the surgery, assessed up to 22 months.
To assess surgical conversion rates in patients who could be surgically resected.
From the first dose to the surgery, assessed up to 22 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of tumor ctDNA
Time Frame: From initial medication to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
To investigate the preliminary antitumor effect of this study and the relationship between ctDNA changes and disease prognosis.
From initial medication to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Gene polymorphism
Time Frame: Within a month of enrollment.
To investigate the polymorphism of UGT1A1 and colorectal cancer genes at baseline.
Within a month of enrollment.

Collaborators and Investigators

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

Sponsor

Shanghai Zhongshan Hospital

Collaborators

CSPC Ouyi Pharmaceutical Co., Ltd.

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)

March 11, 2024

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

January 15, 2024

First Submitted That Met QC Criteria

January 24, 2024

First Posted (Actual)

January 26, 2024

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 17, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSPC-DEY-CRC-K01

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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