Gastrointestinal Neoplasm
Conditions
Keywords
Circulating Tumor DNA, Liquid Biopsy, Gastrointestinal Neoplasm, Metastatic
Brief summary
A study investigating if analysis of circulating tumor DNA (ctDNA) can guide palliative treatment in patients with gastrointestinal cancer.
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)
Interventions
OTHERStandard 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.
OTHERctDNA-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.
Sponsors
Vejle Hospital
Karen-Lise Garm Spindler
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
An open label 1:1 randomized phase II trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compliance with protocol | 3 months | The fraction of participants in ARM B, who comply with the study procedures during the first 3 months after inclusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment cycles | 1 year | Median number of treatment cycles in the two arms during the first 12 month of stuydy participation |
| Response rate Arm A | 1 year | Overall best response and response rate per RECIST during first-line treatment |
| ctDNA response rate Arm B | 1 year | Overall best response and response rate per ctDNA-RECIST during first-line treatment |
Countries
Denmark
Contacts
Primary ContactKaren-Lise G Spindler, MD, Prof
Backup ContactTorben F Hansen, MD, Prof
Outcome results
None listed