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

NCT ID: NCT06300489

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-03
• Study Completion Date: 2025-10-31

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

irinotecan liposomes+capecitabine+chemoradiotherapy

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.

Group Type: EXPERIMENTAL

irinotecan liposomes+capecitabine

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

chemoradiotherapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ji Zhu

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ji Zhu

Role: CONTACT

leo.zhu@126.com

0571-88128152

Dong Liu

Role: CONTACT

liudong@zjcc.org.cn

0571-88128152

Facility Contacts

Ji Zhu

Role: primary

leo.zhu@126.com

0571-88128152

Other Identifiers

CARTOnG-2401

Identifier Type: -

Identifier Source: org_study_id