Consolidative Radiotherapy for Colorectal Cancer Liver Metastases Receiving Surgery or Radiofrequency Ablation

This study is a randomized phase II trial to evaluate the efficacy of adjuvant consolidative radiotherapy in colorectal cancer liver metastasis (CRLM) patients after chemotherapy combined with surgical resection or radiofrequency ablation of liver lesions.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer; Liver Metastases; Radiotherapy
• Intervention / Treatment: Radiation: adjuvant SBRT; Drug: Chemotherapy

Detailed Description

Liver metastases are detected in 40-50% of patients diagnosed with colorectal cancer. Local treatments like surgical resection or radiofrequency ablation result in 5-year survival of 35%. However, relapse still occurs in 70% of patients. Stereotactic body radiotherapy (SBRT) has emerged as a valid treatment not only to provide excellent symptom palliation, but also is effective in local control of metastatic lesions and improves survival. The potential efficacy of SBRT as adjuvant radiotherapy in CRLM patients after surgical resection or radiofrequency ablation is still unknown.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tao Zhang, MD; Phone Number: 862785871982; Email: 1277577866@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Biopsy proven unresectable metastatic colorectal cancer (CRC)
2. Primary resection of colorectal cancer (CRC)
3. Age≥18 years
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Absence of evidence of extra-hepatic diseases
6. 1 to 3 liver metastases with an individual maximum diameter of up to 5 cm
7. Metastatic liver lesions receiving R0 or R1 resection or radiofrequency ablation with visible tumor bed
8. Aspartate aminotransferase, alanine aminotransferase & alkaline phosphates must be ≤ 2.5 times of the upper limit of normal. Total bilirubin must be within the limit of normal.
9. Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm3.
10. Patients must provide verbal and written informed consent to participate in the study.
11. Absence of any severe pulmonary or cardiac diseases

Exclusion Criteria:

1. Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible
2. Patients who are pregnant
3. Patients with severe organ dysfunction
4. History of liver radiotherapy
5. Unwillingness to participate or inability to comply with the protocol for the duration of the study
6. Participation in any investigational drug study within 3 months preceding the start of study treatment
7. Patients not suitable to take part in clinical trials judged by researches

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: chemoradiotherapy; radiotherapy: adjuvant SBRT of liver lesions; chemotherapy: mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment	Radiation: adjuvant SBRT; adjuvant SBRT of liver lesions; Other Names: radiotherapy; Drug: Chemotherapy; mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment; Other Names: neoadjuvant chemotherapy and adjuvant chemotherapy
Active Comparator: chemotherapy; chemotherapy: mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment	Drug: Chemotherapy; mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment; Other Names: neoadjuvant chemotherapy and adjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Evaluate the effect of consolidative SBRT of liver lesions versus observation on disease free survival	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To evaluate overall survival after consolidative SBRT in comparison to observation alone	5 years
Intrahepatic disease free survival	To evaluate Intrahepatic disease free survival after consolidative SBRT in comparison to observation alone	2 years
Toxicities	Acute toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 criteria during and up to 3 months after radiotherapy. Late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for the Research and Treatment of Cancer (EORTC) criteria.	2 years

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China

Publications and helpful links

General Publications

• Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996 Apr 1;77(7):1254-62.
• Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Estimated): June 1, 2021
• Study Completion (Estimated): June 1, 2023

Study Registration Dates

• First Submitted: April 26, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (Actual): May 1, 2017

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 31, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Radiotherapy; Colorectal Cancer; Liver Metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: CRLM-AR1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No