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

Not Applicable

• Conditions: Metastatic Colorectal Cancer
• Interventions: Procedure: Liquid biopsy sampling

• Registration Number: NCT04735900
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2020-09-14
• Study First Submitted: 2020-12-30
• Status Verified: 2021-01
• Study First Submitted QC: 2021-01-29
• Last Update Submitted: 2021-01-29
• Study First Posted: 2021-02-03
• Last Update Posted: 2021-02-03
• Primary Completion: 2022-03
• Study Completion: 2022-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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])

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
First-line FOLFOX/FOLFIRI and panitumumab.	Liquid biopsy sampling	Chemotherapeutic agents will be given as an intravenous infusion at a dose and interval consistent with standard institutional practice.

Primary Outcome Measures

Name	Time	Method
Optimize cutoff value	Start cycle 1 of first-line FOLFOX/FOLFIRI and panitumumab therapy until the day on which the first CT scan is performed following the liquid biopsies taken 9 months after the start of first-line therapy, or when 11 months of follow-up is reached.	Optimization of the cutoff value for NPY methylation in liquid biopsies (ctDNA) in metastatic colorectal cancer patients receiving first-line FOLFOX/FOLFIRI and panitumumab to discriminate between progressive and non-progressive disease as determined by CT scans based on RECIST criteria 1.1. To this end, a Receiver Operating Characteristic (ROC) curve will be developed with data of this study.

Secondary Outcome Measures

Name	Time	Method
Determine progression free and 9-month survival	Start cycle 1 of first-line FOLFOX/FOLFIRI and panitumumab therapy until the day on which the first CT scan is performed following the liquid biopsies taken 9 months after the start of first-line therapy, or when 11 months of follow-up is reached.	To determine the progression free and 9-month survival of RAS and BRAF wild-type metastatic colorectal cancer patients. The progression free survival is defined as time from inclusion to the date of first disease progression per RECIST 1.1 criteria, or death. The 9-month survival will be determined as percentage surviving at 9 months after the start of first-line therapy.

Trial Locations

Locations (6)

AZ Groeninge; 🇧🇪 Kortrijk, Belgium

Antwerp University Hospital (UZA); 🇧🇪 Edegem, Belgium

AZ Maria Middelares; 🇧🇪 Gent, Belgium

AZ Klina; 🇧🇪 Brasschaat, Belgium

AZ Nikolaas; 🇧🇪 Sint-Niklaas, Belgium

GZA; 🇧🇪 Wilrijk, Belgium