Genotype-driven Weekly Irinotecan Liposomes in Combination With Capecitabine-based Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

Phase 1

Recruiting

• Conditions: Rectal Cancer
• Interventions: Drug: irinotecan liposomes+capecitabine

• Registration Number: NCT06300489
• Lead Sponsor: Zhejiang Cancer Hospital

Brief Summary

This study is a multicenter, open, and phase I dose increasing clinical study. Based on the UGT1A1 \* 28 and \* 6 genotypes of patients with locally advanced rectal cancer, determine the dose limiting toxicity (DLT) and maximum tolerable dose (MTD) of weekly irinotecan liposomes in concurrent chemoradiotherapy with capecitabine, investigate the tolerance of irinotecan liposome combined with capecitabine in concurrent chemoradiotherapy with locally advanced rectal cancer, and recommend the dosage for Phase II clinical study，and explore the pharmacokinetic characteristics of irinotecan liposomes combined with capecitabine.At the same time，Preliminary observe the efficacy and safety of irinotecan liposomes combined with capecitabine in chemoradiotherapy.The study plans to recruit 30 patients with advanced rectal cancer who have not received any therapy.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-03
• Study Start: 2024-03-03
• Study First Submitted: 2024-03-03
• Study First Submitted QC: 2024-03-03
• Last Update Submitted: 2024-03-03
• Study First Posted: 2024-03-08
• Last Update Posted: 2024-03-08
• Primary Completion: 2025-01-31
• Study Completion: 2025-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Diagnosed as rectal adenocarcinoma by histopathology, immunohistochemical pMMR or MSI-L, MSS;
2. The baseline clinical stage is T2-4 and/or N+, which is not suitable for initial local resection to achieve curative effect;
3. The distance between the tumor and the anus is<=10cm;
4. No distant metastasis;
5. Age range from 18 to 70 years old, regardless of gender;
6. ECOG PS score 0-1 points;
7. The UGT1A1 * 6 and UGT1A1 * 28 gene phenotypes are all wild-type (GG+6/6), unit point mutant (GG+6/7 or GA+6/6), and dual site mutant (GG+7/7 or AA+6/6 or GA+6/7);
8. Not receiving chemotherapy or any other anti-tumor treatment before enrollment;
9. Able to comply with the protocol during the research period;
10. Sign written informed consent.

Exclusion Criteria

1. Diagnosed as rectal adenocarcinoma by pathological histology, and immunohistochemical dMMR or MSI-H;
2. UGT1A1 * 6, UGT1A1 * 28 gene phenotype three site mutations (AA+7/7 or AA+6/7 or GA+7/7);
3. Pregnant or lactating women
4. Individuals with a history of other malignant diseases in the past 5 years, excluding cured skin cancer and cervical cancer in situ
5. Individuals with a history of uncontrolled epilepsy, central nervous system disease, or mental disorders, whose clinical severity may be assessed by the researcher as hindering the signing of informed consent forms or affecting the patient's adherence to oral medication
6. Clinically severe (i.e. active) heart disease, such as symptomatic coronary heart disease, NYHA grade II or more severe congestive heart failure, or severe arrhythmia requiring medication intervention (see Appendix 12), or a history of myocardial infarction within the past 12 months
7. Organ transplantation requires immunosuppressive therapy
8. Severe uncontrolled recurrent infections or other serious uncontrolled comorbidities
9. The baseline blood routine and biochemical indicators of the subjects do not meet the following criteria: hemoglobin ≥ 90g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; ALT and AST ≤ 2.5 times the normal upper limit value; ALP ≤ 2.5 times the normal upper limit value; Serum total bilirubin<1.5 times the upper normal limit value; Serum creatinine<1 times the upper normal limit value; Serum albumin ≥ 30g/L
10. Known individuals with dihydropyrimidine dehydrogenase (DPD) deficiency
11. Individuals who are allergic to any research medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
irinotecan liposomes+capecitabine+chemoradiotherapy	irinotecan liposomes+capecitabine	There are three dose groups inciuding wild-type (GG+6/6)，unit site mutant (GG+6/7 or GA+6/6) and double sites mutant (GG+7/7 or AA+6/6 or GA+6/7)。Every group will receive irinotecan liposomes injection and capecitabine based chemoradiotherapy.

Primary Outcome Measures

Name	Time	Method
DLT（dose-limiting toxicity）	up to 6 months	Any adverse event that occurs during a research period and is related to Irinotecan liposomes the and meets a certain level or higher of CTCAE.
MTD（maximum tolerable dose）	up to 6 months	the highest dose of exposure to a substance without causing serious toxic reactions.

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China