FOLICOLOR TRIAL: Following Therapy Response Through Liquid Biopsy in Metatstatic Colorectal Cancer Patients

FOLICOLOR is a prospective, randomized, open-label, multicentric phase 3 study evaluating the clinical value of ctDNA-based liquid biopsy in the follow-up of patients receiving first-line therapy for metastatic colorectal cancer.

Patients with confirmed NPY methylation-based ctDNA positivity on an initial liquid biopsy sample will be randomized into two study arms:

• Control arm (CT arm): Treatment decisions are guided by radiographic evaluation using conventional CT scans.
• Study arm (LB arm): Treatment decisions are guided by serial liquid biopsy results.

All patients are followed per study protocol for 18 months from the time of inclusion.

Primary Objective:

To determine whether a liquid biopsy-guided follow-up strategy preserves quality of life (QoL) for longer, by enabling earlier detection of disease progression and more timely therapeutic adjustments, thereby reducing exposure to ineffective treatment and associated toxicity.

Secondary Objectives:

• To evaluate whether liquid biopsy allows earlier detection of progressive disease compared to conventional CT imaging (per RECIST 1.1 criteria).
• To assess time to progression and progression-free survival (PFS) in both the LB arm and CT arm, with progression defined as progressive disease (PD) per RECIST 1.1.
• To evaluate the difference in 3-year overall survival (OS) between both study arms.

Inclusion criteria

• Man or woman ≥ 18 years of age at the time the informed consent is obtained
• ECOG performance status of 0-2
• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum in subjects with unresectable metastatic (M1) disease
• There should be at least 1 uni-dimensionally measurable (min. 10mm) using conventional crosssectional imaging techniques (CT or MRI scan). Lesion must not be chosen from a previously irradiated field, unlessnthere has been documented disease progression in that field after irradiation and prior to randomization. All sites of disease must be evaluated ≤ 28 days prior to randomization
• Adequate hematology, renal, hepatic and coagulation function (at treating physician's discretion)
• Adequate blood results for treatment (at treating physician's discretion)
• Starting a first line treatment

Exclusion criteria

• History of prior or concurrent central nervous system metastases
• History of other malignancy, except:

Malignancy treated with curative intent and with no known active disease present for ≥ 3 years prior to randomization and felt to be at low risk for recurrence by the treating physician.

Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease.

Adequately treated cervical carcinoma in situ without evidence of disease. Prostatic intraepithelial neoplasia without evidence of prostate cancer

• Prior chemotherapy or other systemic anticancer therapy for the treatment of metastatic colorectal carcinoma including but not limited to bevacizumab and anti-EGFR therapy (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib)
• Prior adjuvant chemotherapy (including oxaliplatin therapy) or other adjuvant systemic anticancer therapy including but not limited to bevacizumab and anti-EGFR therapy (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) for the treatment of colorectal cancer ≤ 6 months prior to randomization with the following exceptions: Subjects may have received prior fluoropyrimidine therapy if administered solely for the purpose of radiosensitization for the adjuvant or neoadjuvant treatment of rectal cancer.
• Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities.