Circulating Tumor DNA Guided Adjuvant Chemotherapy for Biliary Tract Carcinoma

Circulating Tumor DNA Guided Adjuvant Chemotherapy for Biliary Tract Carcinoma: A Prospective Clinical Trial

In recent years, circulating tumor DNA (ctDNA)had achieved encouraging results in monitoring recurrence and metastasis after surgery, and has potential clinical application value. The presence of ctDNA after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.

Study Overview

• Status: Not yet recruiting
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: S-1(Intravenous combined with oral)

Detailed Description

The results of the PRODIGE-12/ACCORD-18 study showed that, with a median follow-up of 47 months, the adjuvant chemotherapy arm did not lead to a significant improvement in recurrence-free survival (RFS) and overall survival (OS). Notably, the patients with gallbladder cancer experienced adjuvant chemotherapy significantly worse RFS and OS compared to those in the monitoring arm. ctDNA risk stratifies patients to guide adjuvant treatment decisions This study aimed to demonstrate that a escalation strategy of ctDNA guided adjuvant chemotherapy is superior to standard of care treatment as measured by 2 year disease free survival (DFS) in patients with stage II- III biliary tract cancers with minimal residual disease (MRD) (ctDNA positive).

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jinghan Wang, M.D.; Phone Number: +86-13795362134; Email: wangjinghan@126.com

Study Locations

• China
  • Shanghai, China
    • East Hospital, Tongji University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Patients with pathologically confirmed BTCs according to the UICC/AJCC TNM staging system (8th edition 2017) for stage II-III tumours. Patients eligible for radical resection of BTCs. No synchronous or metastatic malignant tumour found in other organs other than the primary tumor.

  2) Personal status (PS) score as over 80 or Eastern Cooperative Oncology Group (ECOG) score as 0 ~ 2.

  3）With expected survival of more than 12 months. 4) Radical operation performed.

Exclusion Criteria:

• 1) Patients with positive surgical margins and residual lesions after biliary tract tumor surgery.

  2) Blood transfusion performed during operation or within 2 weeks before operation.

  3) Have a history of other malignant tumors within 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group 1: Patients testing negative for ctDNA treated using standard of care treatment; Postoperative ctDNA-negative patients receive oral Teysuno (S-1) for adjuvant therapy。
Experimental: Group 2: Patients with a positive ctDNA test are treated with an escalation strategy; Postoperative ctDNA-positive patients receive intravenous combined oral Teysuno (S-1) for adjuvant therapy。	Drug: S-1(Intravenous combined with oral); Oral combined with intravenous S-1 for ctDNA-positive patients (escalating treatment strategy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA guided adjuvant chemotherapy versus Translational sub study	To demonstrate the superiority of an escalation strategy of ctDNA-guided adjuvant chemotherapy over standard-of-care treatment, 2-year disease-free survival (DFS) was measured as 2-year Disease-Free Survival (DFS) in high-risk stage II-III BTC patients with no evidence of minimal residual disease (ctDNA-negative).	Up to 60 months
Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis	Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis	Up to 60 months
Specificity of postoperative ctDNA in monitoring recurrence and metastasis	Number of patients with ctDNA negative and no recurrence and metastasis confirmed by imaging / number of patients with no recurrence and metastasis confirmed by imaging	Up to 60 months
Accuracy of postoperative ctDNA in monitoring recurrence and metastasis	True positive/ctDNA-positive samples	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	Overall survival of included patients	From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months.
ctDNA clearance rate	The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy	Up to 60 months

Collaborators and Investigators

• Sponsor: Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): November 15, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Estimated): December 14, 2023

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: S-1; circulating tumor DNA (ctDNA)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms
• Other Study ID Numbers: [2023] R&R No. (107)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No