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

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ClinicalTrials.gov Identifier: NCT01097239
Recruitment Status : Withdrawn (Failure to recruit.)
First Posted : April 1, 2010
Last Update Posted : November 20, 2020
Sponsor:
Collaborator:
Imperial College Healthcare NHS Trust
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date  ICMJE March 31, 2010
First Posted Date  ICMJE April 1, 2010
Last Update Posted Date November 20, 2020
Actual Study Start Date  ICMJE November 2009
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 31, 2010)
Quality of life scores (EORTC QLQ-C30 and EORTC QLQ-CR38) [ Time Frame: Within the first 30, 60 and 90 days after HIFU ]
Validated Quality of Life Questionnaire
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2010)
  • Pain relief visual analogue scale [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Examining the Role of Transrectal High Intensity Focused Ultrasound (HIFU) in Rectal Pelvic Cancer
Official Title  ICMJE A Phase I/II Feasibility/Efficacy Study of HIFU in Otherwise Untreatable Pelvic Rectal Cancer
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Rectal Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Vaginal Cancer
  • Cervical Cancer
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: High Intensity Focused Ultrasound
Transrectal High Intensity Focused Ultrasound (HIFU) treatment of the PelvicTumour
Intervention: Device: Sonablate 500 (High Intensity Focused Ultrasound (HIFU))
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: November 18, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: March 31, 2010)
50
Actual Study Completion Date  ICMJE September 2018
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01097239
Other Study ID Numbers  ICMJE 09/H0808/43
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Imperial College London
Study Sponsor  ICMJE Imperial College London
Collaborators  ICMJE Imperial College Healthcare NHS Trust
Investigators  ICMJE
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
PRS Account Imperial College London
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP