Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03595722
Other study ID # 18SM4430
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date July 11, 2019
Est. completion date August 28, 2022

Study information

Verified date August 2019
Source Imperial College London
Contact Ovuefe Efeotor
Phone +447729459614
Email oe408@imperial.ac.uk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The hypothesis of the study is that high intensity focused ultrasound (HIFU) can be used safely to treat rectal and pelvic cancer. The study consists of two trials exploring the use of HIFU in rectal and pelvic cancer to establish the safety and potential efficacy of HIFU in this instance.

The first trial is a feasibility study looking at patients with early rectal cancer. We aim to recruit thirty patients with early rectal cancer who are due to undergo an operation to remove their cancer. After recruiting and consenting them for the trial, we will treat their rectal cancer with HIFU. Approximately one week after treatment they will undergo their normal cancer operation. This will allow us to demonstrate the safety of HIFU as a treatment for rectal cancer and evaluate the changes in rectal and surrounding tissue under the microscope after the cancer is treated with HIFU. In addition, we will monitor patients for any complications and the impact this treatment has on their quality of life. We will monitor the response of various markers for cancer with blood tests.

The second trial aims to evaluate the treatment of a cohort of patients with inoperable rectal cancer. We aim to recruit thirty patients with either inoperable pelvic cancers - rectal, cervical or endometrial, or cancers that have returned after previous operations. We will offer these patients treatment of their cancer using HIFU. We will monitor the symptoms they experience and impact on their quality of life both before and at multiple time points after the treatment with HIFU. We will compare MRI scans before and after treatment to evaluate the effect HIFU has in reducing the size of the cancer. We hope to show that using HIFU in this group of patients can be both effective and lead to an improvement in both their symptoms and quality of life.


Description:

The hypothesis of this study is that high intensity focused ultrasound (HIFU) can be safely and effectively used to treat rectal and advanced pelvic cancers. This study is composed of two feasibility trials to evaluate the safety and efficacy of use in HIFU in early rectal cancer and late pelvic cancer.

The first trial will involve a cohort of 30 patients with early rectal cancer. They will have full work up as per normal care including history, examination, bloods, endoscopy and imaging (CT and MRI scan). Once eligibility has been confirmed, patients will be approached and offered to be enrolled in the study. Once successfully recruited, they will be admitted transrectal HIFU using the Sonatherm (Sonacare Medical, Charlotte, North Carolina, USA) device under general anaesthetic with monitoring for toxicity. Baseline quality of life questionnaires will be filled in by patients prior to HIFU to establish their symptoms prior to treatment. Patients will be admitted for treatment and observed overnight. They will then complete the same questionnaires at two and seven days post HIFU. Blood tests will be taken one week after HIFU administration to monitor levels of tumour markers and inflammatory markers. One week after their HIFU treatment, the patients will undergo their total mesorectal excision (TME) to remove their cancer as per normal treatment protocol. The specimen will be examined to evaluate the histological changes in the tumour and surrounding tissues created by the HIFU. We will be able to quantify the effect of HIFU on the rectal cancer and evaluate for possible thermal damage to surrounding tissues.

Potential patients will be identified during multidisciplinary team (MDT) meetings which include surgeons, radiologists, oncologists and cancer nurse specialists. The team will confirm eligibility and suitability prior to patient recruitment to ensure there is no negative effect on overall patient care due to their involvement in the trial.

The Sonathermâ„¢ systems used ultrasound visualisation to monitor and regulate the HIFU delivery. This allows tissue response to HIFU to be monitored via echogenic changes seen during coagulative necrosis. The strong correlation between echogenic changes and tissue destruction will allow us to alter the power settings if needed to achieve suitable ablation of the target area. A video record of the ultrasound and ablation will be reviewed by the team to evaluate the quality of the ablation performed.

The trial will run for approximately 1 month for each patient: from recruitment into the study to the resection of the cancer. The HIFU dose will cover the entire tumour, the rectal wall, and a 5 mm margin of tissue surrounding the tumour. It is anticipated that all tissue exposed to HIFU, including the rectal wall, will be part of the coagulative necrosis. Antibiotic prophylaxis will be given for five days to reduce the risk of abscess formation and sepsis. Patients will be followed up on day 2 post HIFU and the day of their TME to assess their response to treatment and any complications that develop. Post resection the patients will be followed up as per the normal local guidelines following surgical excision of rectal cancer. They will have their quality of life post resection assessed by completing questionnaires 30 days post resection.

The second part of the study will involve a cohort of 30 patients with either locally advanced pelvic cancer (rectal, endometrial or cervical) or locally recurrent disease. These patients will be unsuitable for operative intervention or any further chemo-radiotherapy treatment. They will have full work up as per normal care including history, examination, bloods, endoscopy and imaging (CT and MRI scan). Once eligibility has been confirmed, patients will be approached and offered to be enrolled in the study. Once successfully recruited, they will be admitted intracavity HIFU using the Sonathermâ„¢ device under general anaesthetic with monitoring for toxicity. Baseline quality of life questionnaires will be filled in by patients prior to HIFU to establish their symptoms prior to treatment. Patients will be admitted for treatment with HIFU and observed overnight to monitor for any toxicity related to treatment with HIFU. Antibiotic prophylaxis will be given for five days to reduce the risk of abscess formation and sepsis. Patients will be followed up closely to monitor for toxicity and any changes in symptom control/quality of life. Patients will complete the same pre-operative questionnaires at multiple time-points post HIFU treatment. Questionnaires will be completed at seven, thirty, sixty and ninety days post HIFU, and three-monthly thereafter. This will enable us to accurately chart the change in quality of life and symptom control created by the HIFU treatment. 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. This will allow comparison with pre-operative imaging to evaluate the effect of HIFU. A video record of the ultrasound and ablation will be reviewed by the team to evaluate the quality of the ablation performed.

Patients will be reviewed at regular intervals after treatment with HIFU to monitor the effect of HIFU on quality of life. Regular blood tests will be taken to monitor tumour markers and markers of systemic inflammation.

Potential patients will be identified during MDT meetings which include surgeons, radiologists, gynaecologists, oncologists and cancer nurse specialists. The team will confirm eligibility and suitability prior to patient recruitment. If felt appropriate by the MDT, patients may be offered a second application of HIFU as necessary.

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date August 28, 2022
Est. primary completion date August 28, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 90 Years
Eligibility Inclusion Criteria:

Early rectal cancer arm:

1. Biopsy proven rectal cancer <15cm from anal verge

2. Targeted region = 3cm in depth dimension, deepest region of tumour = 3.5cm from organ/tissue surface accessible by the probe

3. Tumour accessible by the HIFU probe via suitable acoustic window

4. Early stage disease not requiring neo-adjuvant chemo radiotherapy prior to TME - T1/T2 but confirmed to require adjuvant chemotherapy

5. Ability to undergo an intraluminal ultrasound examination

6. World Health Organisation (WHO) Performance Status 0-3

7. Age =18 and fit for general anaesthetic and HIFU

8. For women of child bearing potential, not pregnant

9. No other serious uncontrolled concomitant illness likely to interfere with treatment or assessment

10. Written informed consent for treatment

Late pelvic cancer arm:

1. Biopsy proven rectal, vaginal, endometrial or cervical cancer (tumour <15cm from anal/vaginal verge)

2. Solid tumour/mass = 3cm in depth dimension, deepest region of tumour = 3.5cm from organ/tissue surface accessible by the probe

3. Lymph node(s) accessible by HIFU for which the primary clinical team advise intervention

4. Tumour accessible by the HIFU probe via suitable acoustic window

5. Partially fixed/unresectable disease and locally advanced disease (T3/T4)

6. Ability to undergo an intraluminal ultrasound examination

7. WHO Performance Status 0-3

8. Age =18 and fit for general anaesthetic and HIFU

9. For women of child bearing potential, not pregnant

10. No other serious uncontrolled concomitant illness likely to interfere with treatment or assessment

11. Written informed consent for treatment

Exclusion Criteria:

Early rectal cancer arm:

1. WHO performance status of 4

2. Uncontrolled cardiac, respiratory or other disease, or any serious medical or psychiatric disorder that would preclude anaesthetic or informed consent

3. Pelvic sepsis

4. Currently enrolled in any neo-adjuvant treatment trial that may induce tumour regression

5. Locally advanced disease - T3/T4 or patients who are not thought to require adjuvant therapy

6. Tumours above peritoneal reflection or below dentate line

7. Subjects with tumours lying < 1cm from sensitive structures/organs

Late pelvic cancer arm:

1. WHO performance status of 4

2. Uncontrolled cardiac, respiratory or other disease, or any serious medical or psychiatric disorder that would preclude anaesthetic or informed consent

3. Pelvic sepsis

4. Currently enrolled in any other palliative treatment trial that may confound results

5. Subjects with tumours lying < 1cm from sensitive structures/organs

Study Design


Intervention

Device:
High Intensity Focused Ultrasound
High intensity focused ultrasound to rectal/pelvic cancer

Locations

Country Name City State
United Kingdom Imperial College London London

Sponsors (2)

Lead Sponsor Collaborator
Imperial College London SonaCare Medical

Country where clinical trial is conducted

United Kingdom, 

References & Publications (6)

Gelet A, Chapelon JY, Bouvier R, Souchon R, Pangaud C, Abdelrahim AF, Cathignol D, Dubernard JM. Treatment of prostate cancer with transrectal focused ultrasound: early clinical experience. Eur Urol. 1996;29(2):174-83. — View Citation

Hill CR, ter Haar GR. Review article: high intensity focused ultrasound--potential for cancer treatment. Br J Radiol. 1995 Dec;68(816):1296-1303. Review. — View Citation

Monzon L, Wasan H, Leen E, Ahmed H, Dawson PM, Harvey C, Muhamed A, Hand J, Price P, Abel PD. Transrectal high-intensity focused ultrasonography is feasible as a new therapeutic option for advanced recurrent rectal cancer: report on the first case worldwide. Ann R Coll Surg Engl. 2011 Sep;93(6):e119-21. doi: 10.1308/147870811X592458. — View Citation

Stewart EA, Gedroyc WM, Tempany CM, Quade BJ, Inbar Y, Ehrenstein T, Shushan A, Hindley JT, Goldin RD, David M, Sklair M, Rabinovici J. Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique. Am J Obstet Gynecol. 2003 Jul;189(1):48-54. — View Citation

Thüroff S, Chaussy C, Vallancien G, Wieland W, Kiel HJ, Le Duc A, Desgrandchamps F, De La Rosette JJ, Gelet A. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003 Oct;17(8):673-7. — View Citation

Wu F, Wang ZB, Chen WZ, Bai J, Zhu H, Qiao TY. Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. J Urol. 2003 Dec;170(6 Pt 1):2237-40. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Complications Complications and toxicity of HIFU treatment 0-30 days
Secondary Symptom control Quality of life questionnaire responses 7-90 days
Secondary Histological tissue changes Histological changes in tumour and surrounding tissue 7-10 days
Secondary Tumour marker changes Changes in circulating tumour markers 7-90 days
Secondary Inflammatory marker changes changes in circulating inflammatory markers 7-90 days
Secondary Radiological changes MRI changes in tumour 30 days
See also
  Status Clinical Trial Phase
Recruiting NCT06223308 - A Study Evaluating the Safety and Efficacy of HB0028 in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Terminated NCT03367871 - Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer Phase 2
Active, not recruiting NCT04537156 - Efficacy, Immunogenicity and Safty Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli) Phase 3
Recruiting NCT03668639 - Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone During Radiotherapy and Concomitant Weekly Cisplatin Phase 2/Phase 3
Active, not recruiting NCT04242199 - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors Phase 1
Withdrawn NCT04806945 - A Phase III Study to Evaluate Efficacy and Safety of First-Line Treatment With HLX10 + Chemotherapy in Patients With Advanced Cervical Cancer Phase 3
Active, not recruiting NCT04185389 - Long-Term Follow-Up of HPV FOCAL Participants
Withdrawn NCT03007771 - Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) Used for Mild Hyperthermia Phase 1
Completed NCT03384511 - The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies. Phase 4
Recruiting NCT05107674 - A Study of NX-1607 in Adults With Advanced Malignancies Phase 1
Completed NCT05120167 - Strategies for Endocervical Canal Investigation in Women With Abnormal Screening Cytology and Negative Colposcopy N/A
Recruiting NCT05483491 - KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer Phase 1
Recruiting NCT05736588 - Elimisha HPV (Human Papillomavirus) N/A
Completed NCT05862844 - Promise Women Project N/A
Recruiting NCT04934982 - Laparoscopic or Abdominal Radical Hysterectomy for Cervical Cancer(Stage IA1 With LVSI, IA2) N/A
Recruiting NCT03876860 - An Enhanced Vaginal Dilator to Reduce Radiation-Induced Vaginal Stenosis N/A
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Completed NCT00543543 - Broad Spectrum HPV (Human Papillomavirus) Vaccine Study in 16-to 26-Year-Old Women (V503-001) Phase 3
Terminated NCT04864782 - QL1604 Plus Chemotherapy in Subjects With Stage IVB, Recurrent, or Metastatic Cervical Cancer Phase 2/Phase 3
Recruiting NCT04226313 - Self-sampling for Non-attenders to Cervical Cancer Screening N/A