Clinical trial NCT06210971: Neoadjuvant Chemoradiation With Nal-IRI and Capecitabine Guided by UGT1A1 Status in Patients With Rectal Cancer
Official title: Exploratory Study on 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: UGT1A1
liposomal irinotecan
total neoadjuvant therapy
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 60
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: 1 week after sugery
Secondary outcomes:
measure: clinical complete response
timeFrame: up to 30 weeks
measure: Major Pathologic Response
timeFrame: 1 week after sugery
measure: Objective Response Rate
timeFrame: through study completion，an average of 3 year
measure: Anal Sphincter Retention Rate
timeFrame: 1 week after sugery
measure: R0 resection rate
timeFrame: 1 week after sugery
measure: 3-year Local Recurrence Free Survival Rate
timeFrame: 3 years
measure: 3-year Progress Free Survival Rate
timeFrame: 3 years
measure: 3-year Overall Survival Rate
timeFrame: 3 years
measure: Incidence of adverse events
timeFrame: 7 months
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hebei Medical University Fourth Hospital
state: Hebei
Study officials:
affiliation: Hebei Medical University Fourth Hospital
name: Fengpeng Wu, Professor
role: PRINCIPAL_INVESTIGATOR
References: