Phase II Study of Irinotecan Liposomes in First-line Treatment of Metastatic Colorectal Cancer

Official title

Phase II Study of Irinotecan Liposomes Combined With 5-FU/LV+ Bevacizumab in First-line Treatment of Metastatic Colorectal Cancer

Overview

To evaluate the objective response rate, disease control rate, progression-free survival, overall survival, surgical conversion rate and safety of irinotecan liposome combined with 5-FU/LV+ bevacizumab regimen in first-line treatment of advanced metastatic colorectal cancer patients.

Detailed description

This is a Phase II clinical study to evaluate the efficacy and safety of the combination regimen of irinotecan liposome injection in the first-line treatment of metastatic colorectal cancer. Patients will receive liposomal injections of irinotecan 70mg/m\^2 d1, bevacizumab 5mg/kg d1, LV 400mg/m\^2 d1, 5-FU 400mg/m\^2, then 2400mg/m\^2, continuous intravenous infusion for 46-48h, d1-2. 86 eligible patients will be enrolled.

Interventions

• Drug Irinotecan Liposome
  70 mg/m\^2 , d1, 14 days per cycle, 8 cycles.
• Drug 5-FU
  5-FU 400mg/m\^2, then 2400mg/m\^2, continuous intravenous infusion for 46-48h, d1-2, 14 days per cycle, 8 cycles.
• Drug LV
  400mg/m\^2, d1, 14 days per cycle, 8 cycles.
• Drug Bevacizumab
  5mg/kg, d1, 14 days per cycle, 8 cycles.

Primary outcome measures

• Objective response rate [Time frame: From initial medication to the date of first documented progression or end of medication or completed 8 cycles treatment, whichever came first . Assessed up to 4 months]

Secondary outcome measures (6)

• Disease control rate [Time frame: From initial medication to the date of first documented progression or end of medication or completed 8 cycles treatment, whichever came first. Assessed up to 4 months]
• Progression free survival [Time frame: From initial medication to the date of first documented progression or end of medication, whichever came first. Assessed up to 30 months.]
• Overall survival [Time frame: From initial medication to the date of death from any cause. Assessed up to 30 months.]
• Percentage of patients undergoing surgery. [Time frame: From the first dose to completed 8 cycles treatment. Assessed up to 5 months.]
• R0 resection [Time frame: From the first dose to the surgery. Assessed up to 6 months.]
• Incidence of adverse events and severity of adverse events as assessed by CTCAE 5.0 [Time frame: From the first dose to completed 8 cycles treatment. Assessed up to 5 months.]

Eligibility criteria

Inclusion criteria

• 18\~85 years old.
• Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma.
• RAS/BRAF v600e mutant or right half colon cancer is known.
• pMMR/MSS is known.
• 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 6 months removed from the date of last administration of neoadjuvant or adjuvant therapy.
• ECOG 0\~1, patients ≥75 years old need an ECOG score of 0
• The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria.
• Normal bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×10\^9/L, platelets (PLT) ≥100×10\^9/L, hemoglobin (Hb) ≥80g/L, albumin (ALB) ≥30 g/L, white blood cells (WBC) ≥3.0×10\^9/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 ≥40 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

• Known or suspected central nervous system metastasis.
• Received irinotecan/irinotecan liposomes/bevacizumab 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 I or below(except hair loss and peripheral neuropathy).
• The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment.
• Severe gastrointestinal dysfunction, gastrointestinal perforation, intraperitoneal abscess, and fistula.
• 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.
• 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 but small amount of ascites on imaging without clinical symptoms could be enrolled.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• West China Hospital，Sichuan University — Sichuan

Identifiers

NCT: NCT06341296 · CSPC-DEY-CRC-K07

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗