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

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Brief Title

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

Official Title

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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Quality of life scores (EORTC QLQ-C30 and/or EORTC QLQ-CR38, EORTC QLQ-CX24, EORTC QLQ-EN24 or EORTC QLQ-OV24)

Secondary Outcome

 Pain relief visual analogue scale

Condition

Rectal Cancer

Intervention

Sonablate 500 (High Intensity Focused Ultrasound (HIFU))

Study Arms / Comparison Groups

 High Intensity Focused Ultrasound
Description:  Transrectal High Intensity Focused Ultrasound (HIFU) treatment of the PelvicTumour

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

0

Start Date

November 2009

Completion Date

September 2018

Primary Completion Date

September 2018

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Paul D Abel, ChM FRCS(Lon) FRCS(Ed), , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT01097239

Organization ID

09/H0808/43


Responsible Party

Sponsor

Study Sponsor

Imperial College London

Collaborators

 Imperial College Healthcare NHS Trust

Study Sponsor

Paul D Abel, ChM FRCS(Lon) FRCS(Ed), Principal Investigator, Imperial College London


Verification Date

November 2020