The ctDNA-RECIST Trial Part One (ctDNA-RECIST)

ctDNA Guided Palliative Systemic Therapy Compared to Standard Care in Metastatic Cancer - The Randomized ctDNA-RECIST Trial

A study investigating if analysis of circulating tumor DNA (ctDNA) can guide palliative treatment in patients with gastrointestinal cancer.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Neoplasm
• Intervention / Treatment: Other: Standard of care; Other: ctDNA-RECIST guided palliative systemic treatment

Detailed Description

Background:

Circulating tumor DNA, (ctDNA) has the potential to better monitor treatment efficacy compared to imaging, possibly sparing the patient for ineffective treatment and their associated toxicity an allowing for an early change of the treatment approach.

Based on multiple dataset we have defined ctDNA-RECIST - the ctDNA response evaluation criteria.

Aim: This phase II randomized trial evaluates the use of ctDNA Response Evaluation Criteria in Solid Tumors (ctDNA-RECIST) versus standard imaging-based RECIST to guide treatment decisions in patients with metastatic gastrointestinal cancers.

Design: Patients are randomized 1:1. Patients in Arm A are offered standard treatment with response evaluation according to the RECIST criteria based on imaging, and treatment pauses according to institutional guidelines.

In Arm B, treatment response is evaluated based on change in ctDNA between the baseline sample and the evaluation and confirmation sample, according to ctDNA-RECIST:

• Progressive disease: An increase of ctDNA above the previous value with no overlap of the two CI's
• Stable disease: A value within CI of the previous value. The category also includes samples with both previous and present value being 0 (undetectable).
• Partial Response: A decrease below the previous value with no overlap of the two CI'S but the lower CI does not overlap 0.
• Complete response: Decreasing value to an undetectable level
• Near complete response: A decrease below the previous value with no overlap of the two CI'S and with the lower CI overlapping 0

Complete and near complete response can be combined and classified as maximal response.

The study is initiated as a feasibility study (part one)and will continue into the expansion trial after interim analysis.(part two)

• Study Type: Interventional
• Enrollment (Estimated): 167
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Karen-Lise G Spindler, MD, Prof; Phone Number: +4591167244; Email: k.g.spindler@rm.dk
• Study Contact Backup: Name: Torben F Hansen, MD, Prof; Email: torben.hansen@rsyd.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Karen-Lise G Spindler
  • Vejle, Denmark, 7100
    • Recruiting
    • Department pf Oncology, Vejle Hospital
    • Contact: Torben F Hansen

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Incurable metastatic gastrointestinal cancer
• Indication for first or second-line systemic treatment
• Measurable disease according to RECIST v.1.1
• CT of chest and abdomen less than 30 days old at time of treatment initiation
• Age at least 18 years
• ECOG performance status 0-2
• Clinically eligible systemic palliative treatment at investigators decision.
• Adequate bone marrow, liver and renal function allowing systemic chemotherapy
• Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable
• Written and verbally informed consent

Exclusion Criteria:

• Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
• Other concurrent malignant tumor except non-melanoma skin cancer or carcinoma in situ cervicis uteri
• Pregnant (positive pregnancy test) or breast-feeding women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A: Standard of care; Response evaluation using imaging-based RECIST according to standard guidelines.	Other: Standard of care; Patients will be offered palliative systemic treatment according to standard of care. Response evaluation will be performed with the imaging-based RECIST according to standard guidelines. Treatment pauses according to institutional guidelines. Blood samples will be analyzed retrospectively to evaluate ctDNA.
Experimental: ctDNA-RECIST guided therapy approach; Response evaluation will be performed using ctDNA-RECIST instead of imaging.	Other: ctDNA-RECIST guided palliative systemic treatment; Patients are offered palliative systemic treatment according to standard of care. Response evaluation will be performed using ctDNA-RECIST. ctDNA is measured before start of treatment. If the baseline sample is ctDNA negative the patient is transferred to an observational cohort, and sampling procedures continues as in the standard arm. If the baseline sample is ctDNA positive the patient continues in the ctDNA-RECIST guided arm. Treatment response is evaluated according to ctDNA-RECIST, and further sampling follows a predefined decision schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance with protocol	The fraction of participants in ARM B, who comply with the study procedures during the first 3 months after inclusion.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment cycles	Median number of treatment cycles in the two arms during the first 12 month of stuydy participation	1 year
Response rate Arm A	Overall best response and response rate per RECIST during first-line treatment	1 year
ctDNA response rate Arm B	Overall best response and response rate per ctDNA-RECIST during first-line treatment	1 year

Collaborators and Investigators

• Sponsor: Karen-Lise Garm Spindler
• Collaborators: Vejle Hospital
• Investigators: Principal Investigator: Karen-Lise G Spindler, MD, Prof, Department of Oncology, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic; Liquid Biopsy; Circulating Tumor DNA; Gastrointestinal Neoplasm
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: KFE 2406

Drug and device information, study documents

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