Rectal Cancer
Conditions
Keywords
UGT1A1, liposomal irinotecan, total neoadjuvant therapy
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.
Interventions
DRUGliposomal irinotecan
Liposomal irinotecan: 50mg/m\^2 or 70mg/m\^2
DRUGCapecitabine
Capecitabine: 625mg/m\^2 or 1000mg/m\^2 bid.
RADIATIONRadiation threapy
50.4Gy/28 fractions
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. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response | 1 week after sugery | Defined as the proportion of patients who have achieved pathologic complete response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| R0 resection rate | 1 week after sugery | Defined as the proportion of patients who have achieved R0 resection. |
| 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. |
| 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. |
| 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORFengpeng Wu, Professor
Hebei Medical University Fourth Hospital
Outcome results
None listed