None listed
Conditions
Brief summary
This study will evaluate the safety and efficacy of External Beam Radiation Therapy (EBRT) in combination with 177 Lu-prostate-specific membrane antigen (Lu-PSMA) theranostic against EBRT alone in patients with recurrent prostate cancer. Who is it for? You may be eligible to join this study if you are a male aged 45 years or above and have a confirmed diagnosis of recurrent prostate cancer following previous radical prostatectomy (RP) with curative intent. Study details Participants will be randomly allocated (by chance) to one of two groups. Participants in one group will undergo external beam radiation therapy (EBRT) in combination with 177Lu-PSMA theranostic treatment. EBRT will be administered daily (on weekdays) over 6.5-7 weeks. 177Lu-PSMA will be administered intravenously in three treatment cycles of once every 8 weeks. Participants in the other group will receive EBRT alone. All participants will be asked to attend 3-monthly follow up visits from the end of treatment for a total period of 24 months, in order to assess treatment response, safety, and health-related quality of life. It is hoped that EBRT delivered together with 177Lu-PSMA will enable the delivery of higher radiation doses to the tumour, resulting in a greater treatment response and improved survival.
Interventions
External beam radiation therapy (EBRT): For patients receiving EBRT, radiotherapy will consist of a conventionally fractionated course of treatment that aims to deliver 66-70 Gy in 33-35 fractions to gross tumour volume and 54 Gy in 33-35 fractions subclinical target volume concomitantly over 6.5-7 weeks using either intensity modulation radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) techniques (as per physician discretion). In general, treatments are delivered daily for a m
External beam radiation therapy (EBRT): For patients receiving EBRT, radiotherapy will consist of a conventionally fractionated course of treatment that aims to deliver 66-70 Gy in 33-35 fractions to gross tumour volume and 54 Gy in 33-35 fractions subclinical target volume concomitantly over 6.5-7 weeks using either intensity modulation radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) techniques (as per physician discretion). In general, treatments are delivered daily for a minimum of 9 and a maximum of 11 fractions per fortnight according to departmental policies, except where interruptions are unavoidable (due to, for example) hospital holidays. Treatments will occur on weekdays only, except for on public holidays. 177Lutetium-prostate specific membrane antigen (177Lu-PSMA): No more than 8 GBq of 177Lu-PSMA is administered intravenously as infusion over 15 to 30 minutes by syringe pump. Dose is administered 8 weekly, over 3 treatment cycles. Patients will receive a dose of 80MBq/kg 177Lu-PSMA at each treatment visit. **This is the approximate mean dose used for all 177Lu-PSMA at all centres administering this therapy around the world. It is based on dosimetric calculation relating to dose limiting organs/dose limiting toxicity (e.g. dose to bone marrow, kidneys, salivary glands etc). The 80 MBq/kg dose is used to prevent (if not - in the worst case scenario - minimise) bone marrow and other toxicity. (NB - this is the same principle used in EBRT). All EBRT and 177Lu-PSMA treatments will take place at GenesisCare treatment sites. Authorised medical personnel will deliver each treatment. **Patients will not receive EBRT and 177Lu-PSMA concurrently. Patients on the combination therapy arm will first receive EBRT. Four weeks later, they will commence 177Lu-PSMA treatment.
Sponsors
GenesisCare
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Written informed consent • Male, aged 45 years or more • Estimated life expectancy of at least 6 months • Eastern Cooperative Oncology Group (ECOG) score 0 or 1 • Previous radical prostatectomy (RP) with curative intent • Biopsy proven prostate adenocarcinoma • Biochemical relapse (any serum PSA level) • Significant avidity (SUVmax of at least 9) on 68Ga-PSMA-ligand PET/CT, with visualised disease confined to the pelvis and outside the prostatic bed • Metastatic lymph nodes not beyond the aortic bifurcation • Androgen deprivation therapy (ADT) naïve • Chemotherapy naïve • Adequate renal function: Cr Cl greater than or equal to 40 mL/min (determined by Cockcroft-Gault formula) • Adequate bone marrow function: platelets greater than or equal to 100 x 109/L (within normal limits); Hb greater than or equal to 90 g/L (within normal limits); neutrophils greater than or equal to 1.5 x 109/L • Adequate liver function: bilirubin < 1.5 x upper limit of normal (ULN); AST, ALT, AP < 2 x ULN; albumin > 30 g/L • Willing and able to comply with all study requirements, including all treatments and pre- and post-treatment assessments • Able to commence treatment within 28 days of randomisation
Exclusion criteria
• Previous external beam radiotherapy to prostatic bed • Bone or visceral metastases • Lymph node metastases above the aortic bifurcation • Presence of > 5 metastatic lymph nodes • Contraindications to pelvic irradiation (e.g., chronic inflammatory bowel disease, previous radiotherapy to pelvic malignancy) • Known hypersensitivity to any isotope of Lu in any chemical form, or any isotope of Ga in any chemical form, or any of the PSMA-targeting ligands • Evidence of urinary tract stricture, or significant urinary incontinence • Presence of active infection at time of screening, or history of serious infection within the previous 4 weeks • Any uncontrolled significant medical, psychiatric or surgical condition (eg. active infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled type 2 diabetes, uncontrolled congestive heart disease, pulmonary disease, etc.), or laboratory findings that, in the opinion of the investigator, might jeopardise the patient’s safety or that would limit compliance with the treatment and assessment requirements of this study • History of any malignancy other than prostate cancer within five years of enrolment (excluding localised non-melanoma skin cancers) • Any mental condition or cognitive impairment that may render the patient unable to adequately understand the requirements, nature and possible consequences of the study
Outcome results
None listed