Neoadjuvant Chemoradiation With Nal-IRI and Capecitabine Guided by UGT1A1 Status in Patients With Rectal Cancer
- Conditions
- Rectal Cancer
- Interventions
- Registration Number
- NCT06210971
- Lead Sponsor
- Hebei Medical University Fourth Hospital
- Brief Summary
This single-arm trial will explore the efficacy and safety of long-course neoadjuvant chemoradiation with liposomal irinotecan and capecitabine guided by UGT1A1 status in patients with locally advanced rectal cancer.
- Detailed Description
This is a single-center, single-arm, prospective clinical study. The aim of this study is to explore the short-term and long-term efficacy and safety of total neoadjuvant therapy with irinotecan liposome in patients with locally advanced rectal cancer. Patients' nutritional status, quality of life, changes in symptoms, and adverse events will also be regularly assessed and registered during the implementation phase of the study, and patients will be treated promptly if symptoms are assessed as positive.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Age: 18~75 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0~1.
- Histopathologically confirmed rectal adenocarcinoma.
- The lower edge of the primary tumor is located below the peritoneal reflection or located ≤ 10 cm above the anal verge.
- Clinical stage: T3-4NanyM0 or T1-2N+M0.
- Adequate bone marrow function as evidenced by: Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count ≥100×10^9/L, Hemoglobin (Hb) ≥90 g/L.
- Adequate hepatic function as evidenced by: Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN, Serum albumin ≥3 g/dL.
- Adequate renal function as evidenced by: Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min.
- Be willing to undergo UGT1A1 gene testing and UGT1A1 genotype of *1*1 or *1*28.
- Accept the neoadjuvant chemoradiotherapy protocol of this study and sign the informed consent.
- Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc.
- Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
- Active HIV infection.
- Combined with uncontrollable systemic diseases.
- History of allergy or hypersensitivity to drug or any of their excipients.
- Any clinical indicators indicating contraindications to radiotherapy/chemotherapy and surgery.
- Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
- Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
- Patients with poor cognitive abilities who are unable to answer questions, fill out questionnaires, or have mental disorders.
- Patients who do not meet the inclusion criteria; patients who meet the inclusion criteria but are not suitable to participate in this trial judged by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Liposomal irinotecan-based TNT therapy liposomal irinotecan Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m\^2 bid + Liposomal irinotecan 50mg/m\^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m\^2 bid d1-7 + Liposomal irinotecan 70mg/m\^2 or 50mg/m\^2, d1, Q2W) before surgery. Liposomal irinotecan-based TNT therapy Capecitabine Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m\^2 bid + Liposomal irinotecan 50mg/m\^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m\^2 bid d1-7 + Liposomal irinotecan 70mg/m\^2 or 50mg/m\^2, d1, Q2W) before surgery. Liposomal irinotecan-based TNT therapy Radiation threapy Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m\^2 bid + Liposomal irinotecan 50mg/m\^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m\^2 bid d1-7 + Liposomal irinotecan 70mg/m\^2 or 50mg/m\^2, d1, Q2W) before surgery.
- Primary Outcome Measures
Name Time Method Pathologic Complete Response 1 week after sugery Defined as the proportion of patients who have achieved pathologic complete response.
- Secondary Outcome Measures
Name Time Method 3-year Local Recurrence Free Survival Rate 3 years Defined as the proportion of patients who are not local recurrence or death at 3 years after enrollment.
clinical complete response up to 30 weeks Defined as the proportion of patients who have achieved clinical complete response.
Major Pathologic Response 1 week after sugery Defined as the proportion of patients who have achieved major pathologic response
Objective Response Rate through study completion，an average of 3 year Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.
Anal Sphincter Retention Rate 1 week after sugery Defined as the proportion of patients who retain anal sphincter
3-year Progress Free Survival Rate 3 years Defined as the proportion of patients who are not progress or death at 3 years after enrollment.
R0 resection rate 1 week after sugery Defined as the proportion of patients who have achieved R0 resection.
3-year Overall Survival Rate 3 years Defined as the proportion of patients who are alive at 3 years after enrollment.
Incidence of adverse events 7 months Use NCI-CTCAE version 5.0 for classification and grading.
Trial Locations
- Locations (1)
Hebei Medical University Fourth Hospital
🇨🇳Shijiazhuang, Hebei, China