Metastatic Colorectal Cancer
Conditions
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.
Interventions
70 mg/m\^2 , d1, 14 days per cycle, 8 cycles.
DRUG5-FU
5-FU 400mg/m\^2, then 2400mg/m\^2, continuous intravenous infusion for 46-48h, d1-2, 14 days per cycle, 8 cycles.
DRUGLV
400mg/m\^2, d1, 14 days per cycle, 8 cycles.
DRUGBevacizumab
5mg/kg, d1, 14 days per cycle, 8 cycles.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | 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 | To investigate antitumor efficacy of study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | From initial medication to the date of first documented progression or end of medication, whichever came first. Assessed up to 30 months. | To investigate antitumor efficacy of study. |
| Overall survival | From initial medication to the date of death from any cause. Assessed up to 30 months. | To investigate antitumor efficacy of study. |
| Disease control rate | 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 | To investigate antitumor efficacy of study. |
| R0 resection | From the first dose to the surgery. Assessed up to 6 months. | To assess surgical conversion rates in patients who could be surgically resected. |
| Incidence of adverse events and severity of adverse events as assessed by CTCAE 5.0 | From the first dose to completed 8 cycles treatment. Assessed up to 5 months. | To assess the incidence and severity of adverse events in combination regimens. |
| Percentage of patients undergoing surgery. | From the first dose to completed 8 cycles treatment. Assessed up to 5 months. | To assess surgical conversion rates in patients who could be surgically resected. |
Countries
China
Contacts
Primary ContactMeng Qiu, MD
Outcome results
None listed