Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Prostatic Neoplasms

Disease Attributes

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Determination of the therapeutic activity of different concentrations of PRX302 at increasing volumes and/or number of deposits per gram of prostate.

PRX302

The purpose of this study is to determine the therapeutic activity of different concentrations of PRX302 at increasing volumes and/or number of deposits per gram of prostate. Therapeutic activity will be determined based on changes in PSA levels, PSA velocity, PSA doubling time and tumor burden following treatment.

An Open-Label, Multi-Center, Phase IIa Trial of PRX302 Treatment of Patients With Locally Recurrent Prostate Cancer After Primary Radiation Therapy

Sophiris Bio Corp

Rosemina Merchant, M.E.Sc., VP, Development and Regulatory Affairs

HDR Brachytherapy implant, Up to 30 Gray (Gy) to target lesion in one to two fractions.

HDR Brachytherapy implant, deliver 1 to 2 fractions, Up to 30 Gray (Gy) to target lesion

HDR Brachytherapy

Beth Chiappetta, BSN

Abhishek Solanki, MD

Matt Harkenrider, MD

Murat Surucu, PhD

Michael Mysz, MS

Hyejoo Kang, PhD

Gopal Gupta, MD

Robert Flanigan, MD

Ahmer Farooq, DO

Kristin Baldea, MD

Steven Shea, PhD

Courtney Hentz, MD

Mark Korpics, MS

Timothy Showalter, MD, MPH

This purpose of this study is to evaluate the safety and effectiveness of a technique called focal high-dose-rate (HDR) brachytherapy as treatment for prostate cancer that has come back in the prostate after prior radiotherapy. The study will examine the safety and efficacy of the treatment. The type of radiation that participants in this research will receive is targeted directly at the areas of the prostate where recurrent disease is evident, while avoiding treatment of the normal appearing prostate. This involves the placement of a radioactive material in the affected area of the prostate temporarily, where it remains for a short period of time, and then is subsequently removed using a minimally invasive technique called HDR Brachytherapy.

The goal of any radiation treatment plan is to achieve maximal disease response with minimal toxicity. HDR brachytherapy offers a promising definitive treatment option in the setting of Locally Recurrent Prostate Cancer after prior definitive radiation, based on the limited data described above, with achievement of biochemical disease control in a large percentage of patients with relatively low toxicity. With focal HDR brachytherapy, the investigators can treat the isolated areas of disease, while avoiding normal prostate tissue, with the goal of further improving toxicity rates. The investigators hypothesize that using single fraction, focal HDR brachytherapy performed with one single implant for the treatment of LRPC is feasible and without excess toxicity, and can be safely delivered. This should allow for better patient convenience and cost and improved treatment dosimetry and planning, as it will decrease the risk of catheter displacement between fractions, which will hopefully correlate to less GU and non-GU acute toxicity. The primary objective is to determine the acute and late GU and GI toxicity of single fraction focal HDR salvage brachytherapy (primary endpoint).

Focal Salvage HDR Brachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy

F-SHARP: A Phase I/II Trial of Focal Salvage High-dose-rate BRachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy

There is no plan to make individual participant data (IPD) available to other researchers

The primary outcome in this study is the number of acute or chronic grade 3-5 toxicities as described by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Loyola University

Assistant Professor of Radiation Oncology

Prostatic Hyperplasia

Hyperplasia

MRI guided transurethral HIFU ablation is targeted to MRI visible, biopsy proven, index lesion(s) within prostate and if possible with 5mm angular extension (imaging based healthy tissue marginal) to both sides from the tumour boundary in transverse plane and 5 mm in coronal plane. The ablative effect is aimed to reach prostate capsule by heating the control boundary (3 mm from capsule) to temperature 57 °C. The focal approach is intended to be radical as for index lesion.

MRI guided transurethral HIFU ablation is targeted to main prostatic malignant tumour squeezing and/or invading the prostatic urethra and/or bladder neck. The approach is intended to be palliative.

MRI guided transurethral HIFU ablation is targeted to MRI visible, biopsy proven, local recurrent index lesion(s) within and/or surrounding prostate and if possible with 5 mm angular extension to either side from the tumour boundary in transverse plane and 5 mm in coronal plane. The approach is intended to be focal and salvage.

The whole-gland HIFU ablation approach will be considered in case of extensive organ confined recurrent prostate cancer (positive biopsies for malignancy from extensive/multiple area in prostate and/or extensive/multiple lesion(s) at baseline MRI) to cover whole prostate.

MRI guided transurethral HIFU ablation is targeted to adenomas of the prostate. The HIFU sector encompasses bilateral (anterolateral) transitional zones between bladder neck and verumontanum (colliculus seminalis).

The technology is developed to ablate targeted benign and malignant prostate tissue through transurethrally inserted probe that transmit ultrasound energy under MRI guidance and control. The therapeutic endpoint of this method is thermal coagulation of prostate tissue.

MRI guided transurethral HIFU ablation of prostatic tissue

Peter Boström, M.D.Ph.D

This study assesses feasibility and safety, the primary outcomes, of MRI guided transurethral high intensity focused ultrasound (HIFU) ablation for prostate diseases (PD). We will enrol 10 patients to each group with criteria as follows: localised prostate cancer (PC); locally advanced PC; locally recurrent PC after external beam radiation therapy (EBRT); benign prostatic hyperplasia (BPH). Secondary outcomes are both oncologic and functional outcomes and imaging based follow up after HIFU therapy will be also assessed.

Prostate cancer (PC) is the most common cancer among men in Finland with the highest incidence of all cancers. Benign prostate hyperplasia (BPH) also has high prevalence, increasing with age. BPH may cause harmful lower urinary tract symptoms (LUTS) and it is demonstrated that by the age of 60, over 50 % of men have clinically significant prostate BPH and up to 40 % of men over age 60 suffer from LUTS.

Currently curative intended therapies for PC, radiation therapy (RT) and radical prostatectomy (RP), offer desirable oncologic local control but have major impact on genitourinary function and quality of life (QoL). Some patients are unfit for surgical procedures or cannot tolerate RT due to concomitant medical conditions or prior therapies. At present lower risk PC is increasingly managed with active surveillance. However, diagnosis of PC and active surveillance itself may both lead to notable psychological and emotional burden impairing QoL. Further, significant amount of cases in some point end up in radical treatment resulted from either risk profile upgrade or patients preference. For these patients optimal treatment might be a focal therapy with sufficient oncologic control and minor impact on QoL.

There is controversy related to optimal treatment in local recurrence after RT. 45% of patients will have local recurrence after RT within 8 years after treatment. Androgen deprivation therapy (ADT) decelerate disease only temporarily and salvage RP includes major risks and is technically demanding, but can provide long-term cure in selected patients.

On the aspect of palliation, there is an eminent need for less invasive supplementary therapies since patients presenting with metastatic or locally advanced PC, generally have low performance status.

Management of benign prostatic obstruction has also faced challenges with conventional treatment modalities, since ageing and profuse co-morbidities among patients have increased. Transurethral resection of prostate (TURP) is still the standard treatment in severe LUTS caused by BPH.

Recently the major development of magnetic resonance imaging (MRI) has been achieved improving PC diagnosis and local staging. Even though PC is often multifocal, evidence indicates that both clinical outcome and prognosis of PC is determined predominantly by index lesion. Because of the notable risk of morbidities involving radical treatments and significant evolution of MRI, focal therapies have attained wide interest. One of the most interesting focal mini-invasive treatment is high intensity focused ultrasound (HIFU). HIFU technique exploits thermal energy; by raising target temperature over 55°C target volume is destroyed due to acute coagulation necrosis. Modern devices delivering HIFU to the prostate are transurethral and emit directional high intensity ultrasound to the focused regions utilising superior MRI guidance compared to older generation ultrasound guidance. Magnetic resonance thermometry technique utilizes noninvasive measurement of tissue temperature allowing monitoring real time temperature changes during treatment. The MRI treatment system is equipped with active dynamic temperature feedback control designed to maintain a constant temperature inside the target volume and at the boundary of the target area. By this way conformal three-dimensional ablative volumes with great spatial accuracy and precision can be achieved simultaneously avoiding damages to the surrounding sensitive tissues. Therapy verification is confirmed instantaneously after treatment by acquiring contrast enhanced MRI (CE-MRI) that visualise the non-perfused-volume (NPV) describing the success of total ablation of the target prostate volume.

This prospective clinical single center feasibility and safety study will evaluate the role of MRI guided transurethral HIFU ablation for various PD and clinical settings. All enrolled patients have prostate pathology and different clinical situation with need of definitive interventions and they are divided to four arms/groups according to specific inclusion criterion. Group 1 localised PC prior to RP, group 2 symptomatic locally advanced PC in need of palliative surgical intervention, group 3 locally recurrent PC after EBRT and group 4 symptomatic BPH in need for intervention.

The hypothesis is that MRI guided transurethral HIFU is feasible and safe in various prostate diseases and clinical settings. If hypothesis is proven for certain or for all groups, the investigators will continue with that group or groups to phase 2 clinical multi-institutional studies.

This study is an early phase 1 non-randomized prospective single-institutional and four arm study to determine the applicability, feasibility and safety of MRI guided transurethral HIFU ablation of prostate separately in each pre-specified group/arm (10 patients per group).

Due to the encouraging feasibility and safety results, an amendment was made to the original study protocol to increase the amount of salvage group patients and BPH group patients. With the approval of the ethics committee, the sample size of the salvage group and BPH group was increased to a total of 40 patients and 30 patients, respectively.

MRI Guided Transurethral HIFU for Various Prostate Diseases

Feasibility and Safety of Transurethral HIFU in Various Prostate Diseases; Particularly Prostate Cancer

Explore and characterise short- and medium-term pattern of S-PSA response following HIFU ablation. Serum PSA will be measured before HIFU ablation and predetermined interval during follow up protocol after HIFU ablation. The serum PSA trend and nadir following HIFU ablation will be demonstrated.

Voiding function is assessed separately in each group/arm by:

- measuring the rate of flow of voided urine using a flowmeter, a device that measures the quantity of urine (volume) voided per unit time (uroflowmetry). The measurement is expressed in millilitres per second (ml/s).

The data from uroflowmetry before and after HIFU ablation will be compared.

Voiding function is assessed separately in each group/arm by:

- post-voided residual urine (PVR) (volume in ml), which estimates the completeness of bladder emptying using a handheld ultrasonic bladder scanner.

The PVR before and after HIFU ablation will be compared.

Evaluation of QoL using standardised questionnaire:

- 26-item short-form version of EPIC, The Expanded Prostate Index Composite

QoL questionnaire before and after HIFU ablation are compared.

The measure is a composite outcome measure reported as single value for each arm/group.

Quality of life questionnaire, International Prostate Symptom Score (IPSS), is used to assess urinary symptoms following HIFU therapy. IPSS consists of seven question concerning urinary symptoms (points from 0 to 5) and one separate question concerning quality of life (points from 0 to 6). The total score of questions related to urinary symptoms can range from 0 to 35. The baseline IPSS score is compared to IPSS scores obtained from predetermined follow up protocol following HIFU therapy to characterise HIFU therapy´s short- (1 week, 3 and 6 months) and medium-term (12 months) impact on lower urinary tract function. A significant change in IPSS is defined as a change of \> 3 points.

The change in total points of IPSS between baseline and most recent follow up visit is measured.

Quality of life questionnaire, International Index of Erectile Function (IIEF-15), is used to assess sexual function following HIFU therapy. A score of 0-5 is awarded to each of the 15 questions that examine 4 main domain of male sexual function: erectile function, orgasmic function, sexual desire and intercourse satisfaction.

Change in total score and each domain of IIEF-15 separately are measured between the baseline and most recent follow-up visit.

The pain is assessed predetermined interval during follow up using Visual Analog Scale for pain (VAS for pain, numerical rating scale 1-10).

The measure is a composite outcome measure reported as single value for each arm/group.

Quantitative analysis of targeting accuracy is defined as spatial difference between target prostate region in treatment planning phase and the target temperature isotherm (57°C) at the end of HIFU treatment on MRI thermometry. The measure used is dice similarity coefficient (DSC - unitless from 0 to 1) which is a statistical validation metric to measure the degree of spatial overlap between two regions.

The measure is a composite outcome measure reported as single value for each arm/group.

Quantitative analysis of targeting accuracy volume illustrates over- and under-treatment representing the amount of tissue ≥ target temperature 57°C outside the target volume and \< target temperature 57°C inside the target volume, respectively.

Over- and under-treatment volumes are expressed as a % of the target volume.

The measure is a composite outcome measure reported as single value for each arm/group.

Quantitative analysis of radiologically verified treatment accuracy; determined by comparing targeting volumes on MRI during treatment planning to immediate, 1 and 3 week NPV in CE-MRI following HIFU therapy. The ratio in percentage (%) between target prostate volume (ml) and NPV (ml) will be measured.

Qualitative analysis of treatment accuracy; determined by comparing both targeting volume on MRI during treatment planning and immediate, 1 and 3 weeks NPV following HIFU therapy separately to histopathologically verified coagulation necrosis volume from the removed prostate at 3 week after HIFU therapy. The ratio in percentage between target prostate volume (ml) and NPV (ml) to coagulative necrosis volume (ml) will be measured.

Quantitative analysis of treatment accuracy; determined by comparing targeting volume on MRI during treatment planning to immediate, 1 week and 12 months NPV in CE-MRI following HIFU therapy.

The ratio in percentage between target prostate volume (ml) and NPV (ml) will be measured.

Quantitative analysis of treatment accuracy; determined by comparing targeting volume on MRI during treatment planning to immediate, 1 week and 12 months NPV in CE-MRI following HIFU therapy.

The ratio in percentage between target prostate volume (ml) and non-perfused volume (ml) will be measured.

Quantitative analysis of treatment accuracy; determined by comparing targeting volume on MRI during treatment planning to immediate, 1 week and 12 months NPV in CE-MRI following HIFU therapy. The ratio in percentage between target prostate volume (ml) and NPV (ml) will be measured.

Safety is determined in each group and all group together by evaluation of the frequency and severity of device/treatment related adverse events associated with the use of TULSA-PRO system to ablate prostate tissue. The severity of the adverse events are graded according to the Clavien-Dindo Classification of surgical complications.

The measure is a composite outcome measure reported as single value for each arm/group.

Histopathological evaluation of the treatment response is based on 2-6-core biopsy results obtained from HIFU treated region/volume at 12 months. The number of biopsies taken is depended on the size and extension of the primary lesion treated with HIFU. The cognitive transrectal ultrasound guided biopsy method will be used to confirm histologically anticipated treatment success; coagulative necrosis/fibrosis/scar tissue of the prostate tissue. The outcome of biopsies (negativity/positivity for prostate cancer) will be measured. The proportion of patients with negative prostate biopsy will be measured at 12 months follow-up visit.

Evaluation and characterisation of image based follow up with repetitive mpMRI (Arm/group 1: immediate, 1 and 3 week, Arms/Groups 2, 3 and 4: immediate, 1 week, 12 month) after HIFU treatment. Image based follow up will be focused on modifications and development of the rim of enhancement surrounding NPV and the evolution of NPV following HIFU treatment.

University of Turku

Turku University Hospital

This group of 12 patients will be given 36Gy of Stereotactic Body Radiotherapy (SBRT) divided into six separate doses. This will be delivered two to three time per week.

This group (12 patients) will be given 38Gy of Stereotactic Body Radiotherapy (SBRT) divided into six separate doses. This will be delivered two to three time per week.

This group (12 patients) will be given 40Gy of Stereotactic Body Radiotherapy (SBRT) divided into six separate doses. This will be delivered two to three time per week.

Each group will have different dose of stereotactic body radiotherapy (SBRT). Depending on which group patients are in.

Stereotactic Body Radiotherapy

Carolyn Kwong

Heidi Tsang

Carol Kwong, RN

Clare Banks, RN

George Hruby

To examine the feasibility, safety and toxicity of focal stereotactic radiation treatment (SBRT) for locally recurrent prostate cancer.

Participants must have biopsy proven locally recurrent prostate cancer. Biopsy will be performed by a Urologist. Participants will have PSMA-PET (prostate-specific membrane antigen and positron emission tomography) scan and MRI in Radiology and Nuclear Medicine by experienced Radiologists in the Royal North Shore Hospital. before starting stereotactic radiotherapy. Participants will require fiducial markers inserted in the prostate and may require hydrogel insertion depending on the location of the recurrence. If these are required, it will be done by experienced radiation oncologists. Fiducial markers insertion involves inserting three gold markers into the prostate. It will be used to locate the prostate accurately during radiation treatment. Hydrogel is a temporary gel being injected into the space between the prostate and rectum to reduce the dose of radiation received by the rectum to minimise side effects from the treatment, Focal Stereotactic Body treatment (SBRT) will be used in the study. There are three groups of participants. Each group will receive different level of radiation dose to test the safety of increasing radiation dose. Group 1 will receive 36 grays (radiation dose unit, Gy)) in 6 treatments. Group 2 will receive 38 grays in 6 treatments and Group 3 will receive 40 grays in 6 treatments. The incremental dose escalation will cease if any excess acute toxicity or late grade 3 toxicity. SBRT will be delivered two to three times per week, every second day. The number of treatments per week will depend on the day of the week participants start their treatment. Participants will be reviewed weekly or second weekly. Toxicity will be recorded. A Safety Committee will be formed containing multi-disciplinary team members. All serious adverse events will be reported to the Principal Investigator and Human Research Ethics Committee within 24 hours.

Group 1 will receive 36 grays (radiation dose unit Gy) in 6 treatments. Group 2 will receive 38 grays (Gy) in 6 treatments and Group 3 will receive 40 grays (Gy) in 6 treatments. If the first group of participants tolerate the treatment well and with minimal side effects, then the next group of participants will be given the same treatment but at the higher dose (38 Gy). If the second group tolerates this higher dose, then the third group of patients will be given a higher dose (40 Gy). This will be the final dose being tested in this investigation.

Focal Radiotherapy for Previously Treated Prostate Cancer Patients

Phase I Feasibility Trial of Stereotactic Re-irradiation of Prostate Cancer Recurrence Within the Definitively Irradiated Prostate

aim to present data in conferences and publications

acute toxicity will be assessed weekly during treatment period to check whether dose escalation can be achieved

outcome will be assessed by reviewing toxicity weekly during the treatment period and at the end of each dose escalation

outcome will be assessed by reviewing toxicity weekly and at the end of each dose escalation

outcome will be assessed by reviewing toxicity weekly or secondly weekly and at the end of each dose escalation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Open-Label, Multi-Center, Phase IIa Trial of PRX302 Treatment of Patients With Locally Recurrent Prostate Cancer After Primary Radiation Therapy	NCT00686088	Locally Recurre...	PRX302	18 Years -	Protox Inc.
Focal Salvage HDR Brachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy	NCT03312972	Locally Recurre...	HDR Brachythera...	18 Years -	Loyola University
MRI Guided Transurethral HIFU for Various Prostate Diseases	NCT03350529	Localised Prost... Locally Advance... Locally Recurre... Benign Prostati...	MRI guided tran...	-	Turku University Hospital
MRI Guided Transurethral HIFU for Various Prostate Diseases	NCT03350529	Localised Prost... Locally Advance... Locally Recurre... Benign Prostati...	MRI guided tran...	-	Turku University Hospital
Focal Radiotherapy for Previously Treated Prostate Cancer Patients	NCT03073278	Locally Recurre...	Stereotactic Bo...	18 Years -	Royal North Shore Hospital
Focal Salvage HDR Brachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy	NCT03312972	Locally Recurre...	HDR Brachythera...	18 Years -	Loyola University

Spots Global Cancer Trial Database for locally recurrent prostate cancer