Colorectal Cancer
Conditions
Keywords
liposomal irinotecan, second-line therapy, metastatic colorectal cancer
Brief summary
This is a multi-center, single-arm study to investigate the efficacy and safety of liposomal irinotecan+5-FU/LV+ bevacizumab as second-line therapy in metastatic colorectal cancer in Chinese population.
Detailed description
Colorectal cancer (CRC) has a poor prognosis and poses a serious threat to human health. FOLFIRI (irinotecan+5-FU/LV) / FOLFOX (oxaliplatin+5-FU/LV) ± angiogenesis inhibitors are common treatments for advanced CRC. For patients receiving oxaliplatin-based therapy, irinotecan-based therapy is recommended as second-line therapy. Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose, improve the efficacy and reduce the toxic side effects. The aim of this study is to explore the efficacy and safety of liposomal irinotecan+5-FU/LV + bevacizumab as second-line treatment for metastatic CRC.
Interventions
DRUGliposomal irinotecan
liposomal irinotecan 70 mg/m²
DRUG5-FU
5-FU 2400 mg/m²
DRUGLV
5-FU 2400 mg/m²
DRUGBevacizumab
bevacizumab 5 mg/kg
Sponsors
Hebei Medical University Fourth Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-75 years old. * Histologically or cytologically proven colon or rectum adenocarcinoma. * Confirmed as unresectable metastatic disease through radiological examination. * At least one measurable lesion (according to RECIST v1.1). * First-line treatment with oxaliplatin-based therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 \ 2. * The expected survival time ≥3 months. * Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10\^9/L. * Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present. * Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria <2+. * Normal coagulation function (INR≤1.5). * Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.
Exclusion criteria
* Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma. * Previous treatment with irinotecan/liposomal irinotecan. * MSI-H/dMMR * Massive pleural effusion or ascites requiring intervention. * Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment. * Active HIV, HBV, HCV infection. * Combined with uncontrollable systemic diseases. * Presence of severe gastrointestinal disease (including active bleeding, > grade 1 obstruction , > grade 1 diarrhea or gastrointestinal perforation) * History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment. * Presence of interstitial pneumonia or pulmonary fibrosis. * Allergy to or intolerance to therapeutic drugs or their excipients;. * History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment. * Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment. * Patients with symptomatic central nervous system metastases. * Documented serum albumin ≤3 g/dL * Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. * Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception. * Participated in other trial within 30 days prior to the first dose of study treatment. * Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug * Patients who are not suitable to participate in this trial for any reason judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 4 months | Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | 4 months | Defined as the percentage of patients who achieved CR, PR, and stable disease (SD) according to RECIST v1.1. |
| Duration of Response | 4 months | Defined as the time from the initiation of a response (first confirmation of CR or PR) to disease progression or death from any cause, whichever occurred first. |
| Progress-free survival | 6 months | Defined as time from the subject's enrollment to first documented disease progression using RECIST version 1.1 by investigator review or death due to any cause, whichever occurred first. |
| Overall survival | 1 year | Defined as the time between signing the informed consent form and death due to various causes. |
| Incidence of adverse events | 5 months | Use NCI-CTCAE version 5.0 for classification and grading |
Countries
China
Contacts
Primary ContactXuhua Hu, Doctor
Outcome results
None listed