None listed
Conditions
Brief summary
The purpose of this study is to assess the use of Prostate-Specific Membrane Antigen (PSMA) PET/CT scans to identify if men with increased Prostate Specific Antigen (PSA) in the blood have prostate cancer cells in the prostate bed alone, elsewhere in the body, or both. The second phase of the study will evaluate the effectiveness of using the Calypso (Registered Trademark) tracking system for radiation therapy. Who is it for? You may be eligible to join this study if you are a male aged 18 years or above, and have undergone radical prostatectomy. To be eligible for the second phase, the PSMA PET scan result must show localised recurrence or be negative for disease. There should be no evidence of metastatic disease on the PSMA-PET. Study details: The study will be divided into two phases. During the first phase all participants will undergo 68Ga-PSMA PET/CT test. This test uses a medical imaging technology called Positron Emission Tomography (PET), a highly sensitive technique using specialised ‘tracer’ particles to detect PSMA. The tracers are given by injection, usually into a vein in the arm. A PET/CT scanner is used to obtain an image showing distribution of the tracer within the body. The PET scan routinely involves a low level CT scan performed at the same time. There is no preparation for a PSMA PET scan. The scan can take 2-3 hours. Before the test, a needle will be inserted into a vein in your arm or hand. A small amount of radioactive tracer will be injected. You will be asked to rest quietly (45-90 minutes). You will then be taken to the PET/CT scanner bed and asked to lie still on the bed while the PET/CT images are taken. This will take about 30 minutes. You will not feel anything while the images are taken. Some people benefit from a sedative if they suffer from a fear of enclosed spaces (claustrophobia). This must be arranged before the scan. Should you need any form of sedation, you will need to fast for 6 hours (nothing to eat or drink) before scan. The amount of radioactivity used for the scan is small and there are no known side effects to the injection. For the second phase of the study, only participants that show no evidence of metastatic disease will receive radiotherapy. Participants with a negative PSMA will be treated to 70Gray (Gy) in 35 fractions at 5 fractions per week with the Calypso tracking system. Participants with a PSMA that is positive for local recurrence only will receive an additional 4Gy in 2 fractions (total dose = 74Gy in 37 fractions at 5 fractions per week). This therapy will use the Calypso tracking system. It uses radiofrequency emitting beacons implanted within the area being treated, allowing tracking of any movement during delivery of radiation. This means that we can make the margins around the cancer smaller thus reducing the side effects of radiation therapy. Participants who are ineligible for Calypso beacons will receive standard radiotherapy (described above), but without Calypso beacons.
Interventions
Screening intervention: Patients presenting with elevated levels of circulating PSA between 0.1-2.5 ng/mL following post-prostatectomy, and fulfilling all other inclusion criteria as outlined in section 5.2.1, will undergo [68Ga] Gallium-labelled PSMA PET/CT imaging. For the PET scan the 68Ga-PSMA ligand will be administered intravenously, and a 68Ga-PSMA PET/CT will be performed 90 minutes post injection (scanning takes approximately 30-40 minutes). A low dose whole-body computed tomography (CT
Screening intervention: Patients presenting with elevated levels of circulating PSA between 0.1-2.5 ng/mL following post-prostatectomy, and fulfilling all other inclusion criteria as outlined in section 5.2.1, will undergo [68Ga] Gallium-labelled PSMA PET/CT imaging. For the PET scan the 68Ga-PSMA ligand will be administered intravenously, and a 68Ga-PSMA PET/CT will be performed 90 minutes post injection (scanning takes approximately 30-40 minutes). A low dose whole-body computed tomography (CT) scan will be performed during the PET scan as this helps to interpret the PET scan. A contrast enhanced CT Chest/Abdo/Pelvis will be performed following the PSMA PET/CT. This is standard care. However, if the imaging centre does not have the ability to perform the contrast enhanced CT Chest/Abdo/Pelvis, the low dose CT will be acceptable. Study participants who report a positive PSMA PET scan for metastatic disease will be screened out and receive appropriate treatment for their metastatic disease off-trial, whilst those who are PSMA PET positive for locally recurrent disease only (macroscopic disease), or those with a negative PSMA (microscopic disease), will be offered a course of salvage radiotherapy utilising implanted Calypso (Registered Trademark) radiofrequency beacons to track movement of the prostate bed in ‘real-time’. Participants who are ineligible for Calypso beacons will be enrolled as a control group receiving the standard radiotherapy treatment described above, but without Calypso beacons. Treatment Intervention: Curative salvage radiotherapy will be undertaken using a series of electromagnetic (EM) transponders (or beacons) that are implanted into the prostate bed then tracked in ‘real-time’ by the Calypso (Registered Trademark) 4D Localisation System (Varian Medical Systems, Palo Alto, CA) during the entire radiation treatment schedule. 1) Prior to treatment, three tiny electromagnetic transponders or beacons — about the size of a grain of rice — will be permanently implanted during a routine day hospital procedure, similar but less invasive than a prostate biopsy. 2) During treatment, an electromagnetic array will be positioned above the treatment site. The array sends a signal that excites the transponders, which then communicates the location of the target. 3) Using harmless non-ionizing electromagnetic waves, the system detects even slight tumour movement in real time and if required, the radiation therapist can pause treatment to make adjustments, so that radiation delivery is once again focused on the tumour. 4) The Varian Calypso (Registered Trademark) system links with our treatment linear accelerators, which produces and delivers the X-rays used to treat cancer. Following beacon insertion, a CT scan will be acquired in order to demarcate the prostate bed region to be ablated with radiotherapy. This is standard practice. The radiation oncologist will then combine clinical judgment with established radiotherapy protocols to define the clinical tumour volume (CTV). Clinical target volumes will be expanded by 3-5mm to create the planning target volume (PTV) and will be treated to 70Gray (Gy) in 35 fractions at 5 fractions per week if they have a negative PSMA. Participantss with a PSMA that is positive for local recurrence only will receive an additional 4Gy in 2 fractions as a boost dose (therefore total dose = 74Gy in 37 fractions at 5 fractions per week). Radiotherapy plans must meet pre-specified dose constraints to normal tissue and relevant organs at risk. Radiotherapy treatment will be delivered using the existing linear accelerators at Epworth Richmond and Freemasons Hospital. The treatments will be adjusted as required based on the biofeedback of the Calypso (Registered Trademark) system to ensure accurate treatment of the clinical target volumes.
Sponsors
Icon Cancer Foundation
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase I (PSMA PET/CT) - Males age 18 years or older. - Patients who have undergone radical prostatectomy for histologically confirmed clinical stage T1- T3 invasive prostate adenocarcinoma. - Post-operative PSA 0.1-2.5ng/ml. - No contraindications to undergoing 68Ga-PSMA-ligand PET/CT (including severe claustrophobia). - ECOG Status 0-2 - Able to undergo intensity modulated radiotherapy. - Patients or their legal representatives must have the ability to read, understand and provide written informed consent. - Able to participate in the stipulated follow-up (either telephone follow-up or on-site visits acceptable, but one follow-up annually should be in person). - Participants capable of child-bearing are using adequate contraception. Phase II (radiotherapy) - No evidence of metastatic disease on PSMA-PET or - localized recurrence on PSMA-PET Inclusion criteria for Calypso beacons - Body habitus enabling Calypso (Registered Trademark) localisation and tracking (as per Calypso (Registered Trademark) Determining a Patient’s Localisation Designation & Orientation before implantation). - Able to undergo Calypso (Registered Trademark) beacon insertion.
Exclusion criteria
- Prostate cancer with significant sarcomatoid, ductal, spindle cell or neuroendocrine small cell components. - Evidence of secondary disease outside the prostate bed. - Previous radiotherapy treatment to the pelvis. - Any other active malignancy (untreated, progressive or recurrent), except for non-melanoma skin cancer. - Any inactive malignancy diagnosed within 5 years of entry, except for non-melanoma skin cancer. - Inflammatory bowel disease (active) such as Crohn’s disease and ulcerative colitis. - Haemorrhagic cystitis. - Known hypersensitivity to 68Ga, PSMA or any of the excipients of 68Ga-PSMA. - Insufficient renal function (eGFR < 30 mL/min/1.73 m2). - Androgen Deprivation Therapy within 6 months prior to enrolment. - Unable to lie flat and/or still during PET-CT. - Patients unable or unwilling to comply with study requirements. - Patients with a history of psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study. Exclusion criteria for Calypso beacon insertion: - Any urogenital anatomic abnormality that would interfere with the ability to access the Calypso (Registered Trademark) beacon insertion site. - Pacemaker or implanted defibrillator. - Presence of hip prosthesis.
Outcome results
None listed