Clinical trial NCT07020468: Neoadjuvant Therapy （NALIRIFOX） for Locally Advanced Colon and Upper Rectal Cancer
Official title: A Clinical Study on the Efficacy and Safety of Oxaliplatin + Irinotecan Liposome + 5-FU/LV as Neoadjuvant Therapy for Locally Advanced Colon and Upper Rectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Colorectal Cancer (CRC)
Keywords: Irinotecan Liposome
Locally Advanced Colorectal Cancer and Upper Rectal Cancer.
Neoadjuvant chemotherapy
Lead sponsor: Affiliated Cancer Hospital of Shantou University Medical College
Sponsor class: OTHER
First posted: 2025-06-13
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Major pathological response rate
timeFrame: 24 months
Secondary outcomes:
measure: Pathological complete response rate
timeFrame: 24 months
Other outcomes:
measure: R0 resection rate
timeFrame: 24months
measure: objective response rate
timeFrame: 24 months
measure: disease-free survival
timeFrame: 24 months
measure: Adverse Event (AE) Incidence Rate
timeFrame: 24 months
Locations:
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
Study officials:
affiliation: Affiliated Cancer Hospital of Shantou University Medical College
name: Muming Xv
role: STUDY_DIRECTOR
References:
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