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

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06300489
• Other study ID #: CARTOnG-2401
• Status: Recruiting
• Phase: Phase 1
• Start date: March 3, 2024
• Est. completion date: October 31, 2025

Study information

• Verified date: March 2024
• Source: Zhejiang Cancer Hospital
• Contact: Ji Zhu
• Phone: 0571-88128152
• Email: leo.zhu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• irinotecan liposomes+capecitabine
Radiotherapy:IMRT DT 50Gy/25Fx. Capecitabine: 625mg/m2 bid po d1-5 qw. For patients are double sites mutant (GG+7/7 or AA+6/6 or GA+6/7),the intial dose of Irinotecan liposomes is 25mg/m2 weekly,for four weeks? This study stratify cases by the "3+3" rule according to UGT1A1 * 6 and UGT1A1 * 28 phenotypes. Three cases were enrolled in each dose group, and if there was no DLT, they were promoted to the next dose group(an increase of 5mg/m2); If there is 1 case of DLT, 3 cases will be reenrolled in the same dose group. If there is no new occurrence of DLT, it will be promoted to the next dose group. Otherwise, the study will be terminated; If there are 2 cases of DLT, the study will be terminated, and the previous dose group will be the maximum tolerated dose (MTD).

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT(dose-limiting toxicity)	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.	up to 6 months
Primary	MTD(maximum tolerable dose)	the highest dose of exposure to a substance without causing serious toxic reactions.	up to 6 months