lead-in FOLICOLOR Trial: Following Therapy Response Through Liquid Biopsy in Metastatic Colorectal Cancer Patients

Detection of progressive disease by neuropeptide Y (NPY) methylation in liquid biopsies in patients with RAS and BRAF wild-type, unresectable, metastatic colorectal cancer receiving first-line treatment FOLFOX/FOLFIRI and panitumumab.

Prospective, multicentric interventional study to optimize the cutoff value of NPY methylation in liquid biopsies in metastatic colorectal cancer patients treated with first-line FOLFOX/FOLFIRI and panitumumab.

Inclusion is possible after histologically or cytologically proven colorectal adenocarcinoma with metastatic lesions according to RECIST 1.1 at the start of first-line treatment using FOLFOX/FOLFIRI and panitumumab. Patient must have a proven RAS and BRAF wild-type tumor.

Patients will be followed by study protocol up to and including the first CT scan following the last liquid biopsies taken, or when a follow-up period of 11 months is reached, until death, until metastasectomy, until lost to follow-up or until (consent) withdrawal.

Eligibility Criteria:
Inclusion Criteria:

* Man or woman ≥ 18 years of age at the time the informed consent is obtained
* Eastern cooperative oncology group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed adenocarcinoma of the colon or rectum in subjects with unresectable metastatic (M1) disease
* At least 1 uni-dimensionally measurable lesion of at least 10 mm per RECIST 1.1 guidelines using conventional techniques (CT scan). Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to inclusion. All sites of disease must be evaluated \<28 days prior to the start of first-line therapy
* Wild-type RAS tumor status (of tumor tissue)
* Wild-type BRAF tumor status (of tumor tissue)
* Adequate hematologic, renal, hepatic and coagulation function
* Starting a first-line treatment with a combination of FOLFOX/FOLFIRI and panitumumab

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 start therapy 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-Epidermal Growth Factor Receptor (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 start therapy 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 start therapy. Subjects must have recovered from all radiotherapy-related toxicities.
* Significant cardiovascular risk
* History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on diagnostic CT scan
* Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria (CTC) grade 2, \[Common Terminology Criteria for Adverse Events (CTCAE) version 5.0\])
* Peripheral sensory neuropathy (≥ CTC grade 2 \[CTCAE version 5.0\])