Study on Predictive Biomarkers of Neoadjuvant Chemoradiotherapy for Rectal Cancer

Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04227886
• Other study ID #: FDRT-011
• Status: Recruiting
• Start date: December 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2020
• Source: Fudan University
• Contact: Ji Zhu, MD
• Phone: +86-2164175590
• Email: leo.zhu[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathological confirmed adenocarcinoma

• Clinical stage T3-4 andor N+

• The distance from anal verge less than 12 cm

• No suspicious metastatic disease (M1)

• ECOG PS 0-1

• UGT1A1*28 6/6 or 6/7

• No previous anti-cancer therapy

Exclusion Criteria:

• Pregnancy or breast-feeding women

• Serious medical illness

• Baseline blood and biochemical indicators do not meet the following criteria:

neutrophils=1.5×10^9/L, Hb=90g/L, PLT=100×10^9/L, ALT/AST =2.5 ULN, Cr= 1 ULN

• DPD deficiency

• UGT1A1*28 7/7

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Fudan University	Harbin Medical University, Liaoning Tumor Hospital & Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TRG	Tumor regression grade	Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy
Primary	Toxicities	Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0	Up to 2 years
Secondary	Overall Survival	The total survival time of the participants from joining the group to the death	3 years
Secondary	Progression-free Survival	The time period that from participants joining the groups to the progression of disease (recurrence or metastasis) or death of any cause.	3 years
Secondary	Local Control rate	The time period that from participants joining the groups to the date of first documented pelvic failure.	3 years
Secondary	pCR	Pathologic Complete Response	Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy