Clinical trial NCT06341296: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

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.

Primary outcomes:
measure: Objective response rate
timeFrame: 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 outcomes:
measure: Disease control rate
timeFrame: 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
measure: Progression free survival
timeFrame: From initial medication to the date of first documented progression or end of medication, whichever came first. Assessed up to 30 months.
measure: Overall survival
timeFrame: From initial medication to the date of death from any cause. Assessed up to 30 months.
measure: Percentage of patients undergoing surgery.
timeFrame: From the first dose to completed 8 cycles treatment. Assessed up to 5 months.
measure: R0 resection
timeFrame: From the first dose to the surgery. Assessed up to 6 months.
measure: Incidence of adverse events and severity of adverse events as assessed by CTCAE 5.0
timeFrame: From the first dose to completed 8 cycles treatment. Assessed up to 5 months.
Other outcomes:
Locations:
city: Sichuan
country: China
facility: West China Hospital，Sichuan University
state: Sichuan, Chengdu
Study officials:
References: