NCT05148767

UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer

Neoadjuvant Chemoradiation With Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer: A Real-Word Multi-center Study

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 606 (estimated)
• Sponsor: Zhejiang Cancer Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

To explore whether the application of irinotecan under the guidance of UGT1A1 gene in neoadjuvant chemotherapy and radiotherapy for locally advanced rectal cancer could improve the clinical efficacy in the real world.

Detailed description

Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is the standard care of treatment for locally advanced rectal cancer (LARC), which could effectively reduce the risk of local recurrence, increase the chance of sphincter preservation, and effectively improve the quality of life of patients. However, only about 8% of patients can benefit from nCRT. Therefore, to improve the therapeutic effect of nCRT and retain the organ function of patients so as to improve their quality of life is the focus of the current investigation. In the previous study, the investigator have completed a series of clinical researches of irinotecan guided by UGT1A1 gene for nCRT in rectal cancer. A dose climbing study was firstly conducted to explore the maximum tolerable dose of irinotecan for nCRT in rectal cancer. The results indicated that the weekly dose intensity of irinotecan could be increased from 50mg/m2 to 80mg/m2 when the genotype of UGT1A1\*28 locus was 6/6, and the weekly dose intensity of irinotecan could also reach 65mg/m2 when the genotype of irinotecan was 6/7 phenotype. Further analysis also demonstrated that there was a dose-effect relationship between the total dose of irinotecan and pathological complete remission (pCR). The recently published CinClare study is a 3-phase randomized controlled trial that doubles the pCR rate and the total CR rate in combination with irinotecan on the basis of capecitabine combined with radiotherapy. However, in the Aristotle study conducted in the United Kingdom at the same phase, it has not been proved that irinotecan could improve the pCR rate, and it is not known whether the difference between the two studies is completely attributed to the irinotecan dose. Therefore, the investigator designed this real-world study to explore whether irinotecan can indeed improve the treatment efficacy in the real world when using irinotecan under the guidance of UGT1A1 gene in nCRT for LARC. Any locally advanced rectal cancer patients treated with irinotecan-based neoadjuvant radiotherapy and chemotherapy can be enrolled in this study. It is expected that the results of this study could provide more basis for individualized treatment of LARC.

Conditions

• Rectal Cancer Stage III

Interventions

Type	Name	Description
DRUG	Neoadjuvant chemoradiotherapy based on irinotecan	Patients with locally advanced rectal cancer treated with irinotecan-based chemoradiotherapy were enrolled in this study. The dose of irinotecan is determined by the genotype of UGT1A1.Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A1\*28 and \*6: 6/6+GG) or 65mg/m2 (UGT1A1\*28 and \*6 ：6/7+GG or 6/6+GA) or 50mg/m2 （UGT1A1\*28 and \*6 ：7/7+GG or 6/6+AA or 6/7+GA）.

Timeline

• Start date: 2022-01-01
• Primary completion: 2026-06-01
• Completion: 2026-12-30
• First posted: 2021-12-08
• Last updated: 2021-12-08

Locations

1 site across 1 country: China