SBRT of Metastases Following Neo-adjuvant Treatment for Colorectal Cancer With Synchronous Liver Metastases

Phase II Single Arm Feasibility Trial to Evaluate Stereotactic Ablative Radiation of Metastases for the Management of Colorectal Cancer With Synchronous Oligo-metastases in Liver

The purpose of this study is to prospectively evaluate the feasibility of SBRT for the management of synchronous oligo metastatic liver metastases from colorectal cancers.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Liver Metastasis Colon Cancer
• Intervention / Treatment: Radiation: stereotactic body radiation treatment (SBRT)

Detailed Description

This will be a phase II feasibility trial to evaluate ablative radiation for the management of colorectal cancer with potentially resectable/ablatabale synchronous oligo-metastases.

In this study, following completion of the neo-adjuvant component of treatment, patients will be re-staged (as is the current standard of care) and can then proceed for SBRT to the liver lesion. Patients who may have responded very well to the systemic treatment with no-residual disease on re-staging imaging, will use pre-treatment imaging for target delineation. The advantage of SBRT is in the minimally invasive approach to treatment that may be associated with lower morbidity, better quality of life and post treatment morbidity, as well as being significantly less expensive.

The planned course of the neo-adjuvant component of treatment for this study will reflect the NCCN (National Comprehensive Cancer Network) guidelines and will treat rectal cancer patients with a short course of radiation followed by 6-9 cycles of a combination chemotherapy regimen.

For the colon cancer group of patients, all patients will receive 6-9 cycles (2-3 months) of neo-adjuvant systemic chemotherapy as per current standard of care.

Patients with non-progressive disease at that point, will have SBRT for the metastatic lesion followed by surgery for the primary rectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aswin Abraham; Phone Number: 780-432-8516; Email: aswin.abraham@albertahealthservices.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
      • Contact: Aswin Abraham; Phone Number: 7804328516; Email: aswin.abraham@albertahealthservices.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• ECOG (Eastern Cooperative Oncology Group) 0-2
• Able to provide written informed consent
• 1-5 Liver lesions with max size of ≤5cm for a single lesion and restricted to one lobe of liver; deemed at Multi-Disciplinary Tumor Board (MDT) to be potentially amenable for SBRT with curative intent
• Liver lesion identified within 3 months of diagnosis of primary and deemed at Multi-Disciplinary Tumor Board (MDT) to be potentially amenable for SBRT with curative intent
• Plan for resection of primary with curative intent
• Patients with liver metastases and potentially resectable/ablatable lung mets can be included.
• Colon cancer patients who have undergone upfront resection of primary colonic lesion can be included
• Able and willing to comply with the terms of the protocol including health-related quality of life (HRQoL) questionnaires
• Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause.
• Females must not be breastfeeding
• Male patients should agree to not donate sperm during the study

Exclusion Criteria:

• Extra-hepatic metastases (except potentially resectable lung mets)
• Not a suitable candidate for liver resection surgery
• Not a suitable candidate for SBRT
• Past history of cancer within 5 years (except basal cell carcinoma)
• Patients who have undergone previous surgery or ablation for liver lesions
• Planned simultaneous resection of primary and liver metastases
• Pregnancy
• Patients with Child-Pugh C and documented cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SBRT to the metastatic liver +/- lung lesions; All rectal cancer patients included in the trial will receive short course radiation to the pelvis (with 25 Gy in 5 fractions) followed by chemotherapy with either 6 cycles of 3 weekly CAPOX chemotherapy or 9 cycles of 2 weekly FOLFOX. All colon cancer patients will receive 6 cycles of 3 weekly CAPOX or 9 cycles of 2 weekly FOLFOX. Patients will proceed for SBRT to the metastatic liver +/_ lung lesions and resection of the colorectal primary. Treatment planning is to be done using CT simulation or conventional simulation (Fluorocscopy) as per institutional practice. Simple beam arrangements, such as parallel opposed beams, are favored wherever possible.

Radiation: stereotactic body radiation treatment (SBRT); SBRT uses 3D imaging to target high doses of radiation to the affected area. There is very little damage to the surrounding healthy tissue. SBRT works by damaging the DNA of the targeted cells. Then, the affected cells can't reproduce, which causes tumors to shrink.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Defined as Time from diagnosis to disease progression at any site or death	From date of diagnosis upto 24 months in follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer Specific Survival (CSS)	Defined as the time from diagnosis to death due to the cancer	Upto 24 months
Overall Suvival(OS)	Defined as the time from diagnosis to death due to any cause .	Expected to be within 3 months post treatment
Toxicity Assessment	Treatment related toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5	Toxicity assessment will be done upto 24 months in follow up
Quality of Life (QOL)C309v3	To study the Quality of Life as measured by QLQ (quality of life questionnaire)-C309v3)	Baseline QOL will be assessed upto 24 months follow up
Quality of Life (QOL)EORTC	To study the Quality of Life as measured by QLQ (quality of life questionnaire)- EORTC CR29 Questionnaire	Baseline QOL will be assessed upto 24 months follow up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory endpoints/outcomes. To identify blood biomarkers that can correlate with disease events	Blood samples will be compared between the baseline and subsequent samples for changes in the expression levels of specific markers that may be associated with metastases and treatment response. These include circulating cell free DNA and exosomes. Carcino Embryonic Antigen (CEA) levels in blood will also be analysed. Micro Satellite Instability (MSI) pattern in the tumor tissue will be evaluated in the pathological tissue	Blood samples will be collected at baseline upto 24 months in follow up

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Investigators: Principal Investigator: Aswin Abraham, Cross Cancer Institute, Alberta Health Services

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: IIT-0023

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