Focal Radiotherapy for Previously Treated Prostate Cancer Patients

Study Overview
=================
Brief Summary
-----------------
To examine the feasibility, safety and toxicity of focal stereotactic radiation treatment (SBRT) for locally recurrent prostate cancer.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Locally Recurrent Prostate Cancer

Intervention / Treatment
-----------------
* Radiation: Stereotactic Body Radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men > 4yrs from external beam radiotherapy (EBRT) meeting the Phoenix definition of biochemical failure or men > 5yrs from EBRT if neo-adjuvant and/or adjuvant androgen deprivation therapy (ADT) also used Recurrence localised to less than 1 lobe of prostate on both PMSA and multi-parametric MRI (less than equal to cT2a) Recurrence must be biopsy proven, with positive biopsies limited to the PET and MRI suspicious region. Life expectancy at least 10yrs from time of SBRT PSA < 10 Exclusion Criteria: Recurrence in immediate proximity to rectum (unless able to have hydrogel) Grade 3 or more toxicity from previous EBRT Contra-indicated for fiducial insertion GS 8,9 or 10 disease previously (relative - consider if decent disease free interval)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>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. | Radiation: Stereotactic Body Radiotherapy<br>* Each group will have different dose of stereotactic body radiotherapy (SBRT). Depending on which group patients are in.<br>|
| Other: Group 2<br>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. | Radiation: Stereotactic Body Radiotherapy<br>* Each group will have different dose of stereotactic body radiotherapy (SBRT). Depending on which group patients are in.<br>|
| Other: group 3<br>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. | Radiation: Stereotactic Body Radiotherapy<br>* Each group will have different dose of stereotactic body radiotherapy (SBRT). Depending on which group patients are in.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility of SBRT dose escalation. This will be assessed by the number of participants with grade 3 acute toxicity according to CTCAE version 4.3 | acute toxicity will be assessed weekly during treatment period to check whether dose escalation can be achieved | at weekly review through completion of each radiothrapy dose level, approximately one year | 
| safety of SBRT dose escalation. This will be assessed by the number of participants with grade 3 acute toxicity according to CTCAE version 4.3 | outcome will be assessed by reviewing toxicity weekly during the treatment period and at the end of each dose escalation | at weekly review through completion of each radiothrapy dose level, approximately one year | 
| Toxicity. This will be assessed by the number of participants with grade 3 acute toxicity according to CTCAE version 4.3 and RTOG toxicity score. | outcome will be assessed by reviewing toxicity weekly and at the end of each dose escalation | at weekly review through completion of each radiothrapy dose level, approximately one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of conservation dose escalation in this cohort of patients | outcome will be assessed by reviewing toxicity weekly or secondly weekly and at the end of each dose escalation | After each group of patients have completed radiotherapy and at 12 and 24 months follow-up. Patients will have routine follow-up 6 monthly for 1 year and then yearly for 10 years post treatment. But study outcomes will only be collected for 2 years. |