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

NCT06225622 | Recruiting Phase 1

• 1 other identifier: CSPC-DEY-CRC-K01
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose

  To investigate the safety.

  Up to 14 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  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 Outcomes (4)

• Objective response rate

  From initial medication to the date of first documented progression or end of medication, assessed up to 20 months.

• Disease control rate

  From initial medication to the date of first documented progression or end of medication , assessed up to 20 months.

• Progression free survival

  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

  From the first dose to the surgery, assessed up to 22 months.

Other Outcomes (2)

• Changes of tumor ctDNA

  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

  Within a month of enrollment.

Study Arms (1)

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

EXPERIMENTAL

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; Drug: Oxaliplatin; Drug: 5-FU; Drug: LV; Drug: Bevacizumab; Drug: Cetuximab

Interventions

Irinotecan Liposome DRUG

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.

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

Oxaliplatin DRUG

85 mg/m2, intravenously infusion, d1, 14 days per cycle, up to 12 cycles.

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

5-FU DRUG

2400mg/m2, intravenous infusion, d1-2, 14 days per cycle. Until the disease progresses or surgery is possible.

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

LV DRUG

400mg/m2, intravenous infusion, d1, 14 days per cycle. Until the disease progresses or surgery is possible.

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

Bevacizumab DRUG

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.

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

Cetuximab DRUG

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.

irinotecan liposome injection combined with oxaliplatin +5-FU/LV+ bevacizumab or cetuximab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• CSPC Ouyi Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

irinotecan sucrosofate; Oxaliplatin; Fluorouracil; Bevacizumab; Cetuximab

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Tianshu Liu, Doctor

CONTACT

+861368 1973 996; liu.tianshu@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Medical oncology

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: January 26, 2024
• Study Start: March 11, 2024
• Primary Completion: January 1, 2026
• Study Completion: May 1, 2026
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

CN (1)