This trial has been designed to prove the feasibility of using liquid biopsy detection of minimal residual disease (MRD) to guide the postsurgical clinical management of early colon cancer patients. Moreover, it is important to define if conventional (CAPOX) versus intensive (FOLFOXIRI) adjuvant chemotherapy could convert plasma ctDNA positive into a ctDNA negative status.
The detection of circulating tumor DNA immediately after surgery with curative-intent identifies minimal residual disease and has been demonstrated as a surrogate of disease-free survival. This finding could guide adjuvant postoperative treatment in early colon cancer patients. The efficacy and safety of FOLFOXIRI were previously tested in metastatic colorectal cancer patients. The Investigators hypothesize that an intensive adjuvant chemotherapy with FOLFOXIRI regimen could convert patients with detectable ctDNA into ctDNA negative indicating appropriate control of minimal residual disease. Moreover, FOLFOXIRI could have a higher conversion rate than conventional CAPOX therapy. The current trial proposes a two-step approach. In the first part, a maximum of 40 patients with positive plasma ctDNA will be receiving an intensive adjuvant treatment with FOLFOXIRI, which is considered at the moment standard of care for metastatic patients. This part will be taken as a go/no go decision. The aim is to get at least 14 patients with ctDNA negative after such adjuvant treatment. If these figures are not met, the trial will be stopped due to futility, recognizing that such adjuvant treatment cannot control MRD. On the other hand, if these numbers are reached, a second part is designed as an exploratory phase II study to further randomize 124 patients with ctDNA positive into CAPOX versus FOLFOXIRI for six months, assessing again ctDNA conversion into a negative status. The aim of this part is to estimate differences in converting plasma ctDNA into negative among the conventional versus intensive adjuvant treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Universitari Vall D'Hebron
Barcelona, Spain
Hospital Universitario Reina Sofía
Córdoba, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain
Hospital General Universitario de Valencia
Valencia, Spain
Proportion of patients with ctDNA clearance following FOLFOXIRI treatment
Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following intensive adjuvant treatment with FOLFOXIRI.
Time frame: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIa).
Difference in ctDNA clearance rate between FOLFOXIRI and CAPOX(FOLFOXIRI) versus conventional adjuvant therapy (CAPOX).
Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following adjuvant chemotherapy, compared between the intensive treatment group (FOLFOXIRI) and the standard-of-care group (CAPOX).
Time frame: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIb).
Disease-free survival in patients with positive ctDNA
Disease-free survival in patients with positive circulating tumor DNA (ctDNA), compared between the FOLFOXIRI and CAPOX treatment groups.
Time frame: At 24 months after the end of treatment (phase IIb).
Disease-free survival according to ctDNA clearance status
Disease-free survival according to ctDNA clearance status (patients with positive ctDNA who become ctDNA-negative versus patients who remain ctDNA-positive), evaluated in each treatment arm.
Time frame: At 12 months after the end of treatment (phase IIb).
Treatment-related toxicity of FOLFOXIRI compared with CAPOX
Incidence and severity of treatment-related adverse events during adjuvant chemotherapy, compared between patients treated with FOLFOXIRI and those treated with CAPOX.
Time frame: During the treatment period and immediately after adjuvant chemotherapy completion (phase IIb).
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), comparing scores between the FOLFOXIRI and CAPOX treatment groups. All scales and single-item measures are transformed to scores ranging from 0 to 100. Higher scores on functional scales represent a higher/healthier level of functioning, and a higher score on the global health status/quality of life scale represents better quality of life. Higher scores on symptom scales or symptom items represent a higher level of symptoms or problems and therefore a worse outcome.
Time frame: At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29)
Colorectal cancer-specific quality of life, functioning, and symptoms will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29), comparing scores between the FOLFOXIRI and CAPOX treatment groups. All scales and single-item measures are transformed to scores ranging from 0 to 100. Higher scores on functional scales represent a higher/healthier level of functioning, whereas higher scores on symptom scales or symptom items represent a higher level of symptoms or problems and therefore a worse outcome.
Time frame: At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.