Clinical Trials – Get involved!

The BURST Research Collaborative would like to encourage its Urological Registrar members to actively participate in ongoing national clinical trials.  BURST is working in collaboration with the Clinical Trials and Statistics Unit at the Institute of Cancer Research (ICR-CTSU) in order to further the research opportunities for BURST members.

We would like to highlight some surgical urology trials that are relevant to our members and would encourage you to assist with patient identification in your current role.

For trainees working at a unit where the trial is open already but you would like to get involved in recruiting patients:

Please discuss this with the principal investigator (PI) at your site to let them know that you are interested in recruiting patients for the study – they will usually be delighted that you have shown an interest. If you will be involved in approaching patients you will need to have Good Clinical Practice (GCP) training (half day online course), need to view the trial site initiation materials and be included on the trial delegation logs. Please contact the trial team using the details below if you need any advice on how to get involved.. If you are able to commit a lot of time to the success of the study at your site, you may ask your PI if he is willing to make you a Co-PI.

For trainees working at a unit where a trial is not open but you would like to participate:

If you are interested in supporting the setup and recruitment to one of these trials and be Co-PI on a study at your site, please discuss the trial with the most relevant Consultant Urologist/Clinician at your unit.  They would need to act as who agrees to be Principal Investigator and agree to oversee study conduct at your Trust. Please contact the trial team using the details below if you need any advice on how to get involved or once you have identified a potential PI at your site to progress with site setup.

Information currently and future recruiting tirals and start and end dates can be found on the UK Clinical Trial Gateway: https://www.ukctg.nihr.ac.uk/home/

Currently recruiting UK-based clinical trials:

InPACT (penile carcinoma)

InPACT is an international phase III trial with a Bayesian design incorporating two sequential randomisations (InPACT-neoadjuvant and InPACT-pelvis) in patients with squamous carcinoma of the penis who have inguinal lymph node metastases (i.e. locally advanced disease). InPACT aims to determine: If there is a role for neoadjuvant therapy in this patient group; and if prophylactic pelvic lymph node dissection (PLND) improves survival in patients at high risk of recurrence following inguinal lymph node dissection (ILND). 400 patients will be recruited (200 from UK sites; 200 US & European sites) over a 5 year period. The Bayesian design will have the following format:

  •      In randomisation 1 (InPACT-neoadjuvant), dependent on disease burden strata, patients are allocated to one of three initial treatment arms:
  1. Standard surgery (ILND) – no neoadjuvant treatment; or
  2. Neoadjuvant chemotherapy followed by ILND; or
  3. Neoadjuvant chemoradiotherapy followed by ILND.
  •      In randomisation 2 (InPACT-pelvis), patients at high risk of relapse (based on histological interpretation of the ILND specimen, patients in both arms will also receive adjuvant chemoradiotherapy, if not already received in the neoadjuvant setting) are randomised to either:
  1. Prophylactic PLND; or
  2. No prophylactic PLND (surveillance).

Trial opened: May 2017, planned recruitment period 5 years.

Contact: inpact-icrctsu@icr.ac.uk


PACE (localised prostate cancer):

PACE is a multicentre, international phase 3 randomised controlled study to assess whether hypofractionated stereotactic body radiotherapy (SBRT) offers therapeutic benefit over prostatectomy (PACE-A) or conventional radiotherapy (PACE-B) in men with early stage, organ-confined prostate cancer. A total of 1716 low–intermediate risk patients with a histological confirmation of prostate adenocarcinoma will be recruited.

  •      PACE A will recruit 858 patients considered candidates for surgery, as agreed by both physician and patient. The participants will be randomised to receive either:
  1. Laparoscopic prostatectomy; or
  2. Prostate SBRT delivered with 36.25 Gy in 5 fractions.
  •      PACE B will recruit 858 patients who are not considered candidates for surgery, or who have declined surgery. These participants will be randomised to receive either:
  1. Conventional radiotherapy (investigators choice between 78 Gy in 39 fractions or 62 Gy in 20 fractions); or
  2. Prostate SBRT delivered with 36.25 Gy in 5 fractions.

Following completion of trial treatment, all participants will be followed up for 10 years.

Trial opened: August 2012, planned recruitment period 8 years.

Contact: pace-icrctsu@icr.ac.uk


iROC Trial (bladder cancer)

The aim of this study is to compare robotic assisted radical cystectomy versus standard open radical cystectomy to see if one gives better recovery times and less complications than the other. Participants are randomised in a 1:1 ratio to one of two groups:

Arm A: Participants undergo a robotically assisted radical cystectomy (RARC).

Arm B: Participants undergo a open radical cystectomy (ORC).

The number of patients aimed for recruitment is 320 (160 per arm).

Trial opened: March 2017, planned recruitment end December 2019.

Contact: situ.iroc@ucl.ac.uk


ATLANTA Trial (prostate cancer)

The aim of this study is to investigate if men with metastatic prostate cancer who undergo treatment of the local tumour in the form of either radical therapy (prostatectomy or radiotherapy) or minimally invasive ablative therapy (MIAT), combined with metastases directly therapy, will have improved survival compared to those who receive standard of treatment alone. They will be investigating this newly evolving treatment paradigm in a formal Three-arm unblinded randomised controlled trial using a positive control.

Intervention Arm 1:

Minimally Invasive Ablative Therapy (MIAT) to prostate in addition to standard of care systemic treatment.

Intervention Arm 2:

Radical therapy with either prostatectomy or external beam radiotherapy.

Metastases Directed Therapy (Intervention Arm 1 and 2):

In both intervention arms 1 and 2, metastases directed therapy (MDT) may be used but intent to use MDT to be declared prior to randomisation.

In total, 80 men will be approached in 10 UK centre to estimate recruitment rate, acceptability of the trial randomisation, reported toxicities and adherence to trial interventions in a pilot phase. They will also be included into the main phase where 918 will be recruited over 30 UK centres. Participants will remain in the study for a maximum of 4 years. The aims are to see whether men will participate in this trial (pilot) before a larger trial (main) is run, and the impact of these treatments on quality of life.

Trial opened: Jan 2019, planned recruitment end Jan 2021.

Contact: atlanta@imperial.ac.uk


NAXIVA Trial (renal cancer)

NAXIVA is a study of axitinib in patients with metastatic and non-metastatic renal cell carcinoma with venous invasion. Patients will be given axitinib (twice daily) for 8 weeks (at an escalated dose) and the response of the venous invasion will be assessed.

The primary objective is to assess the response of the thrombus to axitinib. It is thought that axitinib will reduce the extent of the thrombus in the inferior vena cava will reduce the extent of surgical intervention.

NAXIVA is a single arm, single agent, open label, phase II feasibility study of axitinib in patients with both metastatic and non-metastatic renal cell carcinoma of clear cell histology. 20 patients will be recruited from multiple centres within the United Kingdom

Trial opened: Dec 2017, planned recruitment end Mar 2020.

Contact: NSS.NAXIVA@nhs.net


BladderPath Trial (muscle invasive bladder cancer)

The purpose of the BladderPath trial is to evaluate a new pathway that would largely eliminate transurethral resection of bladder tumour (TURBT) from the initial management of muscle invasive bladder cancer (MIBC) patients. This allows more expeditious treatments for both MIBC (by eliminating delays) and NMIBC (by reducing demand for TURBT). The approach integrates flexible cystoscopy, urine cytology, biopsy and detailed imaging to confirm the diagnosis and stage of disease. Appropriate definitive radical therapy can then be rapidly commenced. Although TURBT is considered a standard part of care for NMIBC, for MIBC it is less obviously essential, particularly for patients undergoing subsequent radical surgery. This study will test the utility of TURBT as a component of care for MIBC in a randomised fashion.

Patients are randomly assigned to either the standard treatment pathway or the image guided pathway (intervention), as described below:

Pathway 1: Standard investigation and initial treatment pathway

Pathway 2: Image-guided pathway – trial intervention arm

Patients have a multi-parametric MRI scan rather than the TURBT. Previous small studies have shown that this scan can distinguish tumours that are confined to the lining (NMIBC) from those that are invading muscle (MIBC). If the scan suggests that the patient has NMIBC, they will be booked for a TURBT as this is the main treatment for this condition. If on the other hand, the scan suggests that the patient has a muscle invasive tumour, they will be booked directly for treatment (chemotherapy, radiotherapy or surgery), without having a TURBT first. The aim is to reduce the time it takes for MIBC patients to receive these other essential and effective treatments. This reduced delay may improve the success of these treatments. This will be one of the main outcome measures of the trial.

Trial opened: Jan 2016, planned recruitment end Jun 2022.

Contact: a.i.hughes@bham.ac.uk


RAFT Study (post-ablative recurrent prostate cancer)

To date, studies have demonstrated very promising outcomes for prostate cancer following focal ablative therapy with the majority of men maintaining their urinary and sexual function after therapy.

In a small proportion of men, disease recurs after focal therapy. The optimal treatment for men with recurrent disease after focal therapy is yet to be defined. Patients may undergo further focal therapy to the recurrent disease, undergo radiation therapy, whole-gland therapy using a minimally invasive approach such as High Intensity Focused Ultrasound (HIFU) or cryotherapy. Alternatively patients may undergo radical surgery where the whole prostate is removed.

The aim of the RAFT study is to characterise the side effects of prostate cancer surgery in men that have undergone prior focal ablation therapy. In addition, the investigators wish to perform a number of basic science studies to attempt to better understand why the patient has experienced recurrent prostate cancer after focal therapy.

Trial opened: Feb 2016, planned recruitment end Dec 2019.

Contact: bci-raft@qmul.ac.uk


FUTURE Study (OAB in females)

Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study); a superiority randomised clinical trial to evaluate the effectiveness and cost effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms.

The study will evaluate whether Urodynamics in patients with refractory OAB improves their treatment outcomes. Patients who fit the criteria for the study and who agree to take part will be randomly allocated to have Urodynamics plus comprehensive clinical assessment or comprehensive clinical assessment only. In both groups, women will be offered standard treatments for refractory OAB as per defined treatment pathways and in accordance with the national guideline.

The investigators aim to recruit 1096 participants across 40 hospitals. The main outcome of the study will be participant reported treatment success measured 15 months post randomisation.

Trial opened: Oct 2016, planned recruitment end May 2020.

Contact: m.abdelfattah@abdn.ac.uk


 

EASE RCC (European Active Surveillance of Renal Cell Carcinoma study)

There is a clear need of information on the growth rate and oncological outcomes of histologically confirmed RCCs by percutaneous biopsy at diagnosis and on the results of a standardized protocol of active surveillance of small RCCs.

The primary objective of this study is to assess overall survival of patients who are diagnosed with incidental, histologically (biopsy) confirmed, <4 cm RCC and are managed conservatively with active surveillance.

A total of 400 patients with small, incidentally detected, histologically confirmed RCCs will be included and data related to the oncological outcomes of an active surveillance approach will be collected.

Trial opened: Aug 2016, planned recruitment end 2020.

Contact: ale.volpe@me.com


STAMPEDE (Locally advanced/metastatic prostate cancer)

STAMPEDE is a multi-centre, randomised controlled trial for patients with locally advanced or metastatic prostate cancer who are commencing long-term Androgen Deprivation Therapy (ADT). Participants can have either newly diagnosed disease, or have been previously treated with radical radiotherapy or surgery but now have signs of progression such as a rising prostate specific antigen (PSA). The trial will assess the effects of adding different agents, both as single agents and in combinations, to the standard-of-care or substituting standard of care. Previous comparisons have investigated the addition of bisphosphonates or docetaxel chemotherapy to standard of care. The multi-arm, multi-stage platform design has so far recruited over 10,000 patients.

The next arm of STAMPEDE (STAMPEDE-oligomets) will investigate whether local therapy (surgery or radiotherapy) plus metastasis-directed therapy improves overall survival as opposed to local therapy alone.

We will update this synopsis as more information becomes available.

Trial opened: Not open as of yet, further details to follow

Contact: mrcctu.stampede@ucl.ac.uk


PUrE (Lower Pole Renal Calculi)

PUrE is a randomised controlled trial with the aim of providing robust evidence to guide clinicians as to whether ESWL, FURS or PCNL is the most suitable (clinically effective and cost effective) for the treatment of people with lower pole kidney stones of varying sizes.

The trial coordinators aim to recruit 1044 patients (522 in each of RCT1 and RCT2) who have a CTKUB confirming the presence of a lower pole renal calculus. Participants will be followed-up by questionnaires sent from the trial office every week up to 12 weeks post intervention and at 12 months post-randomisation. Patients will be randomised depending on the size of calculi present:

RCT1: Patients with stone size <10mm will be randomised to either flexible ureteroensocopy with laser lithotripsy or extracorporeal shockwave lithotripsy.

RCT2: Patients with stone size >10mm and ≤25mm will be randomised to either flexible ureteroensocopy with laser lithotripsy or percutaneous nephrolithotomy.

Trial opened: May 2015, planned recruitment end date of October 2021

Contact: pure@abdn.ac.uk