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

NCT ID: NCT06225622

Last Updated: 2024-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-11
• Study Completion Date: 2026-05-01

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.

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Irinotecan Liposome

Intervention Type: 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.

Oxaliplatin

Intervention Type: DRUG

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

5-FU

Intervention Type: DRUG

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

LV

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: 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.

Cetuximab

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Oxaliplatin

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

Intervention Type: DRUG

5-FU

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

Intervention Type: DRUG

LV

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSPC Ouyi Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tianshu Liu

Head of Medical oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tianshu Liu, Doctor

Role: CONTACT

liu.tianshu@zs-hospital.sh.cn

+861368 1973 996

Facility Contacts

Tianshu Liu, Doctor

Role: primary

Other Identifiers

CSPC-DEY-CRC-K01

Identifier Type: -

Identifier Source: org_study_id