Genotype-driven treatment for advanced rectal cancer

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

This study is testing a new combination of medications for people with advanced rectal cancer to see how safe it is and how well it works based on their genetic makeup.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06300489 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label phase I clinical trial aims to evaluate the safety and tolerability of weekly irinotecan liposomes combined with capecitabine in patients with locally advanced rectal cancer. The study will determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) based on the UGT1A1 genotypes of participants. It will also explore the pharmacokinetic characteristics of the treatment and provide preliminary observations on its efficacy and safety. A total of 30 patients who have not received prior therapy will be recruited for this study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with locally advanced rectal adenocarcinoma who have not undergone prior treatment.

Not a fit: Patients with certain genetic mutations in the UGT1A1 gene or those with distant metastasis will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective and personalized approach to managing locally advanced rectal cancer.

How similar studies have performed: While this approach is novel in its specific genotype-driven methodology, similar studies have shown promise in personalized cancer treatments.

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

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Ji Zhu

Conditions: Rectal Cancer