Magnetic Resonance-Guided High Intensity Focused Ultrasound for Recurrent Rectal Cancer

Magnetic Resonance-Guided High Intensity Focused Ultrasound for Recurrent Rectal Cancer - A Pilot Study

This pilot study hypothesizes that hyperthermia delivered via magnetic resonance-guided focused ultrasound (MRg-FU) is technically feasible and can be safely used in combination with concurrent reirradiation and chemotherapy for the treatment of recurrent rectal cancer. Twenty recurrent rectal cancer patients who are not candidates for surgery will be recruited for hyperthermia treatment delivered via MRg-FU concurrent with reirradiation and oral chemotherapy.

Study Overview

• Status: Completed
• Conditions: Recurrent Rectal Cancer
• Intervention / Treatment: Device: Magnetic resonance-guided focused ultrasound; Radiation: Standard Radiation; Drug: Chemotherapy

Detailed Description

Magnetic resonance-guided focused ultrasound (MRg-FU) is a non-invasive, outpatient modality being investigated for the thermal treatment of cancer. In MRg-FU, a specially designed transducer is used to focus a beam of low intensity ultrasound energy into a small volume at a specific target site in the body. MR is used to identify and delineate the tumour, focus the ultrasound beam on the target and provide real-time thermal mapping to ensure accurate heating of the designated target with minimal effect to the adjacent healthy tissue. The focused ultrasound beam produces therapeutic hyperthermia (40-42°C) in the target field causing protein denaturation and cell damage.

Currently, there is no prospective clinical data reported on the use of MRg-FU in the setting of recurrent rectal cancer. Recurrent rectal cancer is a vexing clinical problem. Current retreatment protocols have limited efficacy. The addition of hyperthermia to radiation and chemotherapy may enhance the therapeutic response. With recent advances in technology, the investigators hypothesize that MRg-FU is technically feasible and can be safely used in combination with concurrent reirradiation and chemotherapy for the treatment of recurrent rectal cancer without increased side-effects.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Able to give informed consent
• Weight <140kg
• Biopsy-proven recurrent rectal adenocarcinoma
• Assessed by the treating surgeon, medical oncologist and radiation oncologist, and following a multidisciplinary discussion, determined to have unresectable and/or inoperable disease in the presence or absence of distant metastases
• Assessed by the treating radiation oncologist and medical oncologist determined to be fit for reirradiation and chemotherapy
• Prior pelvic radiotherapy
• Target lesion visible by MR
• Target lesion accessible for MRg-FU procedure
• Target lesion maximum dimension ≤ 6cm
• Able to communicate sensation during MRg-FU treatment

Exclusion Criteria:

• Abdominal or pelvic surgery (excluding biopsy) ≤ 6 weeks prior to study enrolment
• Chemotherapy or other systemic anti-cancer agent ≤ 6 weeks prior to enrolment
• Previous radiotherapy ≤ 6 weeks prior to enrolment
• Recurrent tumour involves small bowel
• Unable to characterize pain
• Pregnant / Nursing woman
• Orthopaedic implant along proposed MRg-FU beam path or at site of target lesion.
• Serious cardiovascular, neurological, renal or hematological chronic disease
• Active infection
• Unable to tolerate required stationary position during treatment
• Allergy to MR contrast agent or sedation

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: MRg-FU; Hyperthermia via magnetic resonance-guided focused ultrasound will be administered once per week for three weeks concurrent with standard radiation and chemotherapy.

Device: Magnetic resonance-guided focused ultrasound; Targeted warming of the tumor via 3 weekly MR-guided ultrasound procedures. Concurrent with radiation and chemotherapy.; Other Names: MRg-FU; Radiation: Standard Radiation; 30.6 Gray (Gy) over 17 fractions concurrent with chemotherapy (institutional standard).; Other Names: Radiation Therapy; Drug: Chemotherapy; 3.5 weeks concurrent with radiation therapy (institutional standard).; Other Names: Xeloda; Oral capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicities	Gastrointestinal and genitourinary toxicities assessed as per Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 after each MRg-FU treatment and 30, 60 and 90 days post-treatment.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late toxicities	Gastrointestinal and genitourinary toxicities assessed as per CTCAE v4.0 every 6 months post-treatment for three years.	3 years
The efficacy of MRg-FU in reducing pain	Patient reported pain will be assessed through completion of the Brief Pain Inventory (BPI) and reporting of analgesic usage after each MRg-FU treatment, monthly post-treatment for three months and every 6 months post-treatment for 3 years.	3 years
Patient quality of life	Patient reported quality of life will be assessed through completion of the European Organization for Research and Treatment of Cancer (EORTC) Functional Assessment of Cancer Therapy - Colorectal (FACT-C) questionnaire after each MRg-FU treatment, monthly post-treatment for three months and every 6 months post treatment for 3 years.	3 years
Assessment of radiologic response following treatment.	Assessment of response using the EORTC Response Evaluation Criteria in Solid Tumors (RECIST) criteria.	3 years

Collaborators and Investigators

• Sponsor: William Chu, MD, MSc, FRCPC
• Collaborators: Philips Medical Systems
• Investigators: Principal Investigator: William Chu, MD, FRCPC, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: August 18, 2015
• First Posted (Estimated): August 19, 2015

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: 273-2011; 226861 (Other Identifier: Health Canada)