Colorectal Cancer (CRC)
Conditions
Keywords
Irinotecan Liposome, Locally Advanced Colorectal Cancer and Upper Rectal Cancer., Neoadjuvant chemotherapy
Brief summary
The goal of this clinical trial is to evaluating the efficacy and safety of Oxaliplatin + Irinotecan Liposome + 5-FU/LV in patients with Locally Advanced Colorectal Cancer and Upper Rectal Cancer. Patients would be included as:1. Aged between 18-75 years, with no gender restrictions; 2. Biopsy pathology confirmed as advanced colon cancer and upper rectal cancer; 3. Clinical staging of T3N+ or T4Nany with initially resectable tumors; 4. No distant metastasis observed in routine chest and abdominal CT scans. The main question it aims to answer is Major Pathological Response Rate, referring to the proportion of patients who experience a significant reduction in the size of their tumor or near-complete pathological regression after treatment, typically assessed through a biopsy or surgical resection. Participants will be Chemotherapy administered before surgery, with 3-6 cycles of treatment, using the chemotherapy regimen of Oxaliplatin + Irinotecan Liposome + 5-FU/LV.
Detailed description
This study is a single-center, single-arm, prospective clinical trial. A total of 57 patients are expected to be enrolled over 24 months, with a 1-year follow-up observation period. Eligible participants who meet the inclusion criteria and do not meet the exclusion criteria will receive neoadjuvant treatment with irinotecan liposome combined with oxaliplatin + 5-FU/LV (NALIRIFOX). Treatment will be administered in 2-week cycles for 3-6 cycles, and surgery will be planned for those who meet surgical criteria. For those who do not meet surgical criteria, the subsequent treatment plan will be decided by the investigator. Postoperative adjuvant therapy will be determined by the investigator based on the patient's condition. The primary endpoint is the major pathological response (MPR) rate, and secondary endpoints include pathological complete response (pCR), R0 resection rate, objective response rate (ORR), disease control rate (DCR), disease-free survival (DFS), and safety. Patients would be included as:1. Aged between 18-75 years, with no gender restrictions; 2. Biopsy pathology confirmed as advanced colon cancer and upper rectal cancer; 3. Clinical staging of T3N+ or T4Nany with initially resectable tumors; 4. No distant metastasis observed in routine chest and abdominal CT scans.
Interventions
DRUGNALIRIFOX
The patients with Locally Advanced Colorectal Cancer and Upper Rectal Cancer will undergo neoadjuvant treatment with irinotecan liposome combined with oxaliplatin + 5-FU/LV (NALIRIFOX), with each treatment cycle lasting 2 weeks, for a total of 3-6 cycles.
Sponsors
Affiliated Cancer Hospital of Shantou University Medical College
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
1. Aged 18-75 years, both male and female are eligible; 2. ECOG score of 0-1; 3. Biopsy-confirmed pathological diagnosis of advanced-stage colon cancer or upper rectal cancer; 4. Clinical staging of T3N+ or T4Nany with initially resectable disease; 5. Routine chest and abdominal CT scans show no distant metastases; 6. Bone marrow function: neutrophils (ANC) ≥1.5×10\^9/L, platelets (PLT) ≥100×10\^9/L, hemoglobin (Hb) ≥70g/L; 7. Liver function: ALT, AST ≤2.5×ULN (upper limit of normal); total bilirubin ≤1.5×ULN; serum albumin ≥3 g/dL; 8. Kidney function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated using Cockcroft-Gault formula); 9. For female patients and those with reproductive potential, a negative pregnancy test must be conducted ≤72 hours prior to starting the study treatment, and they must agree to avoid pregnancy during the study treatment and for 6 months after the study treatment. For male patients with reproductive potential partners, they must agree to use adequate, medically approved contraception during the last study treatment and for 90 days afterward; 10. Must be willing to undergo the neoadjuvant chemotherapy regimen in this study and sign an informed consent form.
Exclusion criteria
1. Patients who have had other malignant tumors within the past 5 years (except for cured and non-recurring carcinoma in situ, basal cell carcinoma of the skin, etc.); 2. Patients with active, uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, defined as persistent signs/symptoms related to infection that do not improve despite appropriate antibiotics, antiviral therapy, and/or other treatments; 3. Patients with uncontrolled systemic diseases, including unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmias, history of severe pericardial disease, and other cardiovascular diseases; uncontrolled hypertension (defined as a systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg despite standardized antihypertensive treatment), or a history of hypertensive crisis or hypertensive encephalopathy; uncontrolled diabetes (fasting blood glucose ≥10 mmol/L); 4. Patients who are known to be allergic or intolerant to the investigational drug or its excipients in this study; 5. Any clinical indicators showing contraindications for chemotherapy and surgery; 6. Patients using strong inhibitors or inducers of CYP3A4, CYP2C8, and UGT1A1, etc.; 7. Pregnant or breastfeeding women, and women of childbearing potential who refuse to use appropriate contraception during the trial; 8. Patients who have participated in other clinical trials within 4 weeks prior to enrollment; 9. Patients deemed unsuitable for participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major pathological response rate | 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate | 24 months | The Pathological Complete Response Rate (pCR) is typically expressed as a percentage (%). It refers to the proportion of patients in whom no cancer cells are detected in the tumor tissue after treatment, as assessed by pathological evaluation, indicating a complete response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate | 24months | R0 resection rate is expressed as a percentage (%). It refers to the proportion of patients who can undergo a surgical resection (removal of a tumor or tissue) where the margins of the resected tissue are free from cancerous cells after the intervention of Oxaliplatin + Irinotecan Liposome + 5-FU/LV. |
| objective response rate | 24 months | Objective response rate (ORR)is expressed as a percentage (%). It refers to the proportion of patients whose cancer shrinks or disappears after treatment, including complete Response (CR) or partial Response (PR).ORR= Number of patients with CR+ PR /Total number of patients in the study. |
| disease-free survival | 24 months | Disease-Free Survival (DFS) refers to the period during which a patient shows no evidence of the disease returning or progressing after they have received treatment. The unit of Disease-Free Survival is typically time, and it is most often measured in months or years. |
| Adverse Event (AE) Incidence Rate | 24 months | The Adverse Event (AE) Incidence Rate，as assessed by CTCAE v5.0，refers to the frequency or rate at which adverse events occur in a clinical trial or patient population.AE Incidence Rate= Number of patients experiencing at least one adverse event / Total number of patients in the study. |
Countries
China
Outcome results
None listed