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

Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06341296
• Other study ID #: CSPC-DEY-CRC-K07
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 2024
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: West China Hospital
• Contact: Meng Qiu, MD
• Phone: 028-85423203
• Email: qiumeng33[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 86
• Est. completion date: December 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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: ? 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; ? 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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Irinotecan Liposome
70 mg/m^2 , d1, 14 days per cycle, 8 cycles.
• 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.
• LV
400mg/m^2, d1, 14 days per cycle, 8 cycles.
• Bevacizumab
5mg/kg, d1, 14 days per cycle, 8 cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
West China Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	To investigate antitumor efficacy of study.	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	Disease control rate	To investigate antitumor efficacy of study.	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	Progression free survival	To investigate antitumor efficacy of study.	From initial medication to the date of first documented progression or end of medication, whichever came first. Assessed up to 30 months.
Secondary	Overall survival	To investigate antitumor efficacy of study.	From initial medication to the date of death from any cause. Assessed up to 30 months.
Secondary	Percentage of patients undergoing surgery.	To assess surgical conversion rates in patients who could be surgically resected.	From the first dose to completed 8 cycles treatment. Assessed up to 5 months.
Secondary	R0 resection	To assess surgical conversion rates in patients who could be surgically resected.	From the first dose to the surgery. Assessed up to 6 months.
Secondary	Incidence of adverse events and severity of adverse events as assessed by CTCAE 5.0	To assess the incidence and severity of adverse events in combination regimens.	From the first dose to completed 8 cycles treatment. Assessed up to 5 months.