Exploratory Study in Achievement of Improved Survival by Molecular Targeted Chemotherapy and Liver Resection for Not Optimally Resectable Colorectal Liver Metastases (ATOM ES)

An Exploratory Study to Evaluate Biomarkers as Predictive and /or Prognostic Factors of Benefit From Randomized Phase ll Study of mFOLFOX6+Bevacizumab or mFOLFOX6+Cetuximab in Liver Only Metastasis From KRAS Wild Type Colorectal Cancer

The correlation between the values of angiogenesis-related growth factors in plasma and efficacy, and biomarkers relevant as prognostic factors or predictive factors for sensitivity or resistance to treatment will be examined exploratively.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Liver Metastasis
• Intervention / Treatment: Drug: Bevacizumab; Drug: L-OHP; Drug: l-LV; Drug: 5-FU; Drug: 5-FU; Drug: Cetuximab

Detailed Description

The correlation between the values of angiogenesis-related growth factors in plasma and efficacy, and biomarkers relevant as prognostic factors or predictive factors for sensitivity or resistance to treatment will be examined exploratively.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 162-0814
      • EPS Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who registered the ATOM trial and signed informed consent prior to initiation of any trial-specific procedure and treatment.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mFOLFOX + Bmab; mFOLFOX plus bevacizumab	Drug: Bevacizumab; 5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Avastin; Drug: L-OHP; 85 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Oxaliplatin; Drug: l-LV; 200 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Levofolinate; Drug: 5-FU; 400 mg/m2 intravenous bolus on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Fluorouracil; Drug: 5-FU; 2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Fluorouracil
Active Comparator: mFOLFOX + Cmab; mFOLFOX plus cetuximab	Drug: L-OHP; 85 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Oxaliplatin; Drug: l-LV; 200 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Levofolinate; Drug: 5-FU; 400 mg/m2 intravenous bolus on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Fluorouracil; Drug: 5-FU; 2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Fluorouracil; Drug: Cetuximab; 250 mg/m2 intravenously administered over 60 minutes (400 mg/m2 over 120 minutes as the initial dose) on day 1 and day 8 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the values of angiogenesis-related growth factors in plasma with Progression-free survival (PFS)	To evaluate the values of angiogenesis-related growth factors in plasma with PFS centrally assessed	Baseline, Cycle 8, Progression Disease

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the correlation of values of angiogenesis-related growth factors in plasma with efficacy and adverse events	Response rate, Tumor shrinkage rate, Liver resection rate, R0 liver resection rate( pathologically confirmed ), Progression-free survival(CT/MRI image assessed by the attending physician), Time to treatment-failure, Overall survival, Incidence of adverse events (drag-related, surgery-related) , Exploratory endpoints	Baseline, Cycle 8, Progression Disease
Progression-free survival among the RAS wild type subpopulation		assessed every 8 weeks, up to 4 years
Exploratory analysis of the relevance of tumor size and expression level of angiogenesis-related growth factors in plasma		Baseline, Cycle 8, Progression Disease

Collaborators and Investigators

• Sponsor: EPS Corporation
• Investigators: Principal Investigator: Ichinosuke Hyodo, MD, PhD, Graduate School of Comprehensive Human Sciences, Tsukuba University, Department of Gastroenterology; Principal Investigator: Yoshihiro Kakeji, MD, PhD, FACS, Kobe University Graduate School of Medicine, Division of Gastrointestinal Surgery, Department of Surgery

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: April 14, 2013
• First Submitted That Met QC Criteria: April 14, 2013
• First Posted (Estimate): April 17, 2013

Study Record Updates

• Last Update Posted (Actual): August 2, 2017
• Last Update Submitted That Met QC Criteria: August 1, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Liver only metastasis from KRAS Exon 2 wild type; Liver only metastasis from RAS wild type
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Fluorouracil; Oxaliplatin; Bevacizumab; Cetuximab
• Other Study ID Numbers: ATOM Exploratory study; UMIN000010429 (Other Identifier: UMIN)