Clinical trial NCT06300489: Genotype-driven Weekly Irinotecan Liposomes in Combination With Capecitabine-based Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
Official title: Genotype-driven Phase I Study of Weekly Irinotecan Liposomes in Combination With Capecitabine-based Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Rectal Cancer
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2024-03-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: DLT（dose-limiting toxicity）
timeFrame: up to 6 months
measure: MTD（maximum tolerable dose）
timeFrame: up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: