Examining the Role of Transrectal High Intensity Focused Ultrasound (HIFU) in Rectal Pelvic Cancer

November 18, 2020 updated by: Imperial College London

A Phase I/II Feasibility/Efficacy Study of HIFU in Otherwise Untreatable Pelvic Rectal Cancer

This is a single centre pilot trial to establish the feasibility and role of endoluminal HIFU in patients with locally advanced cancer within the pelvis that is either primary or recurrent and with all available current therapy inappropriate and/or exhausted.

The aim is to make a preliminary assessment of efficacy & dosage for evaluation in a randomised controlled trial. Whilst efficacy data are limited in a small feasibility study; radiological, biochemical and histopathological analysis of the patient and patient specimens, along with quality of life questionnaires (QoL), will be used to provide preliminary measures of efficacy in this patient cohort.

These analyses will allow examination of the biochemical, metabolomic and histological changes associated with HIFU treatment in cancer within the pelvis.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

CURRENT TREATMENT OF LOCALLY ADVANCED PELVIC CANCER Colorectal cancer This is a common condition with about 40,000 new cases a year in the United Kingdom. The optimal multimodality management of stage III & IV rectal cancer remains an increasing challenge. There is a high risk of local recurrence and poor survival has been reported for patients treated by surgery alone. About 20% of patients may present with locally advanced tumours, which are partially or totally fixed (T3/T4). Until recently there have been no widely accepted and validated methods of defining preoperatively either locally advanced rectal cancer or unresectable disease. The use of pre-operative pelvic magnetic resonance imaging (MRI) to predict the likelihood of achieving an R0 resection (Beets-Tan et al 2001, Brown et al 2003) has resulted in improved selection. Pre-operative chemoradiotherapy can downstage locally advanced tumours, and result in higher resection rates being achieved with reduced risk of local recurrence (Bosset et al 1993, Rich et al 1995).

Gynaecological cancers Treating other advanced pelvic malignancies including vaginal, ovarian, endometrial and cervical cancers is similarly challenging. Disease recurrence at the site of surgical resection or adjacent lymph nodes can also preclude further curative options, due to chemotherapy resistance, reaching maximum safe radiotherapy limits or unsuitable surgical options.

It is proposed that High Intensity Focused Ultrasound (HIFU) may become another modality of treatment in locally advanced or unresectable pelvic disease.

RATIONALE FOR PERFORMING THE STUDY Colorectal cancer This is the third most common cause of cancer and cancer death in both men and women (40,000 cases and just under 16 000 deaths per year in the UK). Worldwide, there are approximately 1 million cases and 500 000 deaths per annum. Primary treatment is usually surgical with, in appropriate cases, adjuvant or neo-adjuvant therapy currently including radiotherapy, cytotoxic chemotherapy or a combination. Unfortunately, the overall survival of locally advanced disease is at best 50%. Many patients who have residual, refractory or recurrent rectal cancer experience serious morbidity from local tumour invading and destroying adjacent tissues including bone, nerves (sacrum), bladder and the skin. These interfere severely with normal daily activities, especially bowel function and cause great distress in terms of pain, with many patients requiring permanent palliative colostomies.

Gynaecological cancers Other advanced pelvic malignancies can be equally problematic to manage successfully. Annually in the UK, approximately 250 vaginal cancer, 7000 ovarian cancer, 8000 endometrial cancer and 3000 cervical cancer diagnoses are made, with some being incurable at the time of presentation. Treatment options include surgery, hormonal therapy, chemotherapy, radiotherapy or a combination, although palliative patients can often be left with debilitating symptoms including severe pain and fistula formation, compromising their quality of life.

High Intensity Focused Ultrasound (HIFU) is a method of accurately delivering ablative ultrasound (US) generated high temperatures non-invasively or endo-luminally focused to specific areas in the body using imaging (ultrasound or MR) guidance. Intracavitary or endo-luminal (also called transrectal) HIFU has been appraised by the National Institute for Clinical Excellence (NICE) in the treatment of prostate cancer. It is currently used for primary prostate cancer; there is also evidence it may be effective in treating post-radiotherapy prostate cancer recurrence. Short and medium term data demonstrate that HIFU may be equivalent to some current prostate cancer therapies but with reduced morbidity and length of stay. As the prostate and rectum are adjacent there is now a natural evolution to translate the success in prostate to the adjacent rectum/other pelvic structures.

There is a large unmet clinical need for new treatments for patients with residual or progressing local pelvic cancer (such as rectal in origin as well as other pelvic malignancies) in whom all current therapies are exhausted. Intracavitary HIFU offers such a therapy.

An initial cohort of 20 patients will be offered intracavitary HIFU using the Sonablate 500 (Sonacare Medical, Charlotte, NC, USA) intra-luminal device (at different, escalating energy doses) under general anaesthetic with monitoring for toxicity and ablative efficacy using pre and post-treatment Imaging.

As none of the intracavitary devices have yet been used in rectal, vaginal, ovarian, endometrial, cervical or pelvic lymph node tumours directly (but have been used in the rectum to treat prostate cancer), it is important that to gauge the levels of energy and resultant cancer tissue destruction from a variety of different treatment energies. In this manner, the first phase of this trial is equivalent to the 'dose escalation' phase of a drug trial.

Once the optimum energy levels, safety and treatment protocol are known, a further 30 patients will be treated in Phase II. Patients will undergo MR Imaging pre- and post-treatment to objectively assess the tumour and will complete quality of life questionnaires, pain scores, and functional questionnaires. Survival data will be documented. Post-treatment imaging will be performed at between 3-4 weeks, as within this time frame the ablative effect (a necrotic area) as seen in prostate cancer treated by HIFU, will become clearer providing useful data for the Phase I element.

The trial will run in two stages: the end of the first phase (for regulatory requirements) is defined as 30 days from the date that the last patient has completed trial therapy. The non-interventional follow-up stage will then commence in which patients are followed up for a minimum of 6 months or death.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • London, England, United Kingdom, W12 0HS
        • Imperial College Healthcare NHS Trust (Hammersmith Hospital)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Biopsy proven rectal, vaginal, ovarian, endometrial or cervical cancer (tumour <15cm from anal/vaginal verge)
  • Lymph node(s) accessible by HIFU for which the primary clinical team advise intervention
  • Partially fixed/unresectable disease and locally advanced disease (T3/T4)
  • Patient considered to be unsuitable for or have exhausted all currently available therapies
  • WHO Performance Status 0-2
  • Fit for general anaesthetic and HIFU
  • Not pregnant
  • No other serious uncontrolled concomitant illness likely to interfere with treatment or assessment
  • Written informed consent for treatment

Exclusion Criteria:

  • WHO performance status of 3 or more
  • Uncontrolled cardiac, respiratory or other disease, or any serious medical or psychiatric disorder that would preclude anaesthetic or informed consent
  • Pelvic sepsis
  • Currently enrolled in any other treatment trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High Intensity Focused Ultrasound
Transrectal High Intensity Focused Ultrasound (HIFU) treatment of the PelvicTumour
Device: Sonablate 500 (High Intensity Focused Ultrasound (HIFU))
High Intensity Focused Ultrasound (HIFU) Delivered by the Sonablate 500 Transrectal Device
Other Names:
  • Sonablate 500
  • HIFU

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life scores (EORTC QLQ-C30 and/or EORTC QLQ-CR38, EORTC QLQ-CX24, EORTC QLQ-EN24 or EORTC QLQ-OV24)
Time Frame: Within the first 30, 60 and 90 days after HIFU
Validated Quality of Life Questionnaire
Within the first 30, 60 and 90 days after HIFU

Secondary Outcome Measures

Outcome Measure
Time Frame
Pain relief visual analogue scale
Time Frame: Within the first 30, 60 and 90 days after HIFU
Within the first 30, 60 and 90 days after HIFU
Tumour marker changes (CEA and CA19.9)
Time Frame: Within the first 30, 60 and 90 days after HIFU
Within the first 30, 60 and 90 days after HIFU

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

Imperial College Healthcare NHS Trust

Investigators

  • Principal Investigator: Paul D Abel, ChM FRCS(Lon) FRCS(Ed), Imperial College London
  • Study Chair: Leonardo Monzon, BSc MBBS MRCS(Eng), Imperial College Healthcare NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2009

Primary Completion (Actual)

September 1, 2018

Study Completion (Actual)

September 1, 2018

Study Registration Dates

First Submitted

March 31, 2010

First Submitted That Met QC Criteria

March 31, 2010

First Posted (Estimate)

April 1, 2010

Study Record Updates

Last Update Posted (Actual)

November 20, 2020

Last Update Submitted That Met QC Criteria

November 18, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09/H0808/43

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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