OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer - (OPTIPAL-II)

OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer - Feasibility Study Investigating Circulating Tumor DNA for Treatment Decisions

The present study will investigate the feasibility and clinical value of using circulating tumor DNA as selection for anti-epidermal growth factor receptor treatment for metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic; KRAS Gene Mutation; Circulating Tumor DNA; BRAF Gene Mutation; NRAS Gene Mutation; Epidermal Growth Factor Receptor Inhibitor
• Intervention / Treatment: Other: Plasma circulating DNA analysis

Detailed Description

The primary aim of this prospective study is to investigate if cfDNA in plasma is feasible and reliable for selection of mCRC patients who will benefit of anti-EGFR monoclonal antibody therapy

Secondary, to analyze developments in mutational status as reflected by cfDNA in plasma during therapy and at time of progression

• Study Type: Observational
• Enrollment (Actual): 49

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic colorectal cancer and indication for palliative chemotherapy with potential anti-EGFR monoclonal antibody.

Description

Inclusion criteria

• Histopathologically verified metastatic colorectal cancer
• Indication for systemic palliative treatment with standard Anti-EGFR monoclonal antibodies
• Fit for therapy with EGFR inhibition
• Consent to treatment and sampling
• Measureable disease according to RECIST v 1.1
• Age ≥ 18

Exclusion criteria

• PS > 2
• Significant other cancer disease within 5 years of inclusion
• Conditions precluding sampling during therapy and treatment breaks.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Colorectal cancer patients; Clinical utility of ctDNA analysis for treatment decision Use of ctDNA for KRAS, NRAS and BRAF testing prior to potential anti-EGFR monoclonal antibody treatment for metastatic colorectal cancer	Other: Plasma circulating DNA analysis; Clinical utility of ctDNA analysis for treatment decision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of ctDNA analysis for RAS mutation analysis	Feasibility measures Identification of wildtype or mutated status and results delivered to clinicians; Initial clinical test results i.e. ctDNA mutations or wildtype status within 7 days; Detailed mutation type characterization is provided retrospectively. Failure parameters; Quality of samples; PB > 5%, CPP1 major loss < 10%; Transportation > 3 week days; Analysis > 3 working days; Total results delivered > 7 days.	maximum 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retrospective concordance analysis	Retrospective comparison of tumor mutation and plasma mutation analysis at baseline	By end of study, expected after 3 years
Disease control rate	Rate of disease control	1 year
OS	Overall survival rate	3 years
Resistance mutations	Rate of Ectoderm mutations at time of progression	At time of progression, data analysis expected after 3 years
Lead time	Calcualted lead time between radiologically detected progression and molecular biologically detected ( by Ectoderm and other resistance mutations) in the ctDNA.	At time of progression, data analysis expected after 3 years

Collaborators and Investigators

• Sponsor: Karen-Lise Garm Spindler
• Investigators: Study Chair: Karen-Lise G Spindler, Department of Oncology, AUH, Dk

Publications and helpful links

General Publications

• Callesen LB, Sorensen BS, Pallisgaard N, Laugesen IG, Boysen AK, Spindler KG. Total cell-free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay. Mol Clin Oncol. 2022 Mar;16(3):64. doi: 10.3892/mco.2022.2497. Epub 2022 Jan 17.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): February 3, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: KFE1713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No