The ctDNA-RECIST Trial Part One

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)

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