NCT04227886

Study on Predictive Biomarkers of Neoadjuvant Chemoradiotherapy for Rectal Cancer

A Prospective, Observational, Multicenter Study on Biomarkers for Predicting the Efficacy and Toxicities of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Based on Tissue and Plasma Exosome RNA

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 250 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Backgrounds: A multicenter randomized phase III trial (NCT02605265) proved that adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable. Purposes: This study aims to identify the predictive biomarkers (from patients' tumor biopsy samples and peripheral blood samples before neoadjuvant therapy) for predicting the response and toxicities to neoadjuvant therapy to stratify patients and optimize treatment strategy.

Detailed description

OBJECTIVES: Primary: * Establish a predictive model for response based on tissue RNA and plasma exosome RNA * Establish a predictive model for toxicities based on tissue RNA and plasma exosome RNA Secondary: * Internal validation of the established predictive models * External validation of the established predictive models OUTLINE: -Treatment: Patients receive neoadjuvant therapy and surgery per the protocol. Samples collection Tumor tissue and peripheral blood will be collected prior to neoadjuvant therapy. -Grouping: Response: Patients will be dichotomized into two groups based on the TRG. TRG of 0-1 is defined as good response. TRG of 2-3 is defined as poor response. Toxicities: Patients will be dichotomized into two groups based on the grade of AEs. No grade 3-4 toxicities occurs during neoadjuvant therapy is defined as light toxicities. Grade 3-4 toxicities occur during neoadjuvant therapy is defined as heavy toxicities. -Predictive Model Construction: Using RNA sequencing method to obtain the whole genome transcription profiles of the tumor tissue and plasm exosome RNA. Compare the gene expression differences between the two response groups and the two toxicity groups. Predictive models of response and toxicities are constructed. -Internal Validation: Patients treated at Fudan University Shanghai Cancer Center (N=50) per the protocol will be enrolled as the internal validation cohort. Samples of tissue and plasm will be collected and analyzed. The performance of the model will be evaluated by the correlation of the predicted response/toxicities and the actual response/toxicities. -External Validation: Patients treated at Liao'ning Cancer Hospital \& Institute (N=50) and Harbin Medical University Cancer Hospital (N=50) per the protocol will be enrolled as two external validation cohorts. Samples of tissue and plasm will be collected and analyzed. The performance of the model will be evaluated by the correlation of the predicted response/toxicities and the actual response/toxicities.

Conditions

• Rectal Neoplasm Malignant Carcinoma
• Chemoradiotherapy
• Neoadjuvant Therapy
• Predictive Biomarkers
• Adenocarcinoma

Interventions

Type	Name	Description
RADIATION	Radiation	Neoadjuvant radiotherapy consisted of 50 Gy in 25 fractions using intensity-modulated radiotherapy to the primary tumor and to mesorectal, presacral, and internal iliac lymph nodes.
DRUG	Capecitabine-Irinotecan Combination	The concurrent chemotherapy consists of capecitabine 625 mg/m2 twice daily 5 days per week and combined with weekly irinotecan. The irinotecan dose was used based on UGT1A1 genotype of 80mg/m2 for UGT1A1\*1\*1 or 65mg/m2 for UGT1A1\*1\*28 weekly, followed by a cycle of XELIRI.

Timeline

• Start date: 2019-12-01
• Primary completion: 2020-12-31
• Completion: 2021-12-31
• First posted: 2020-01-14
• Last updated: 2020-01-14

Locations

1 site across 1 country: China