Testing the addition of new treatments to standard treatment in prostate cancer that has spread to other areas of the body
- Conditions
- Metastatic hormone-sensitive prostate cancerCancer
- Registration Number
- ISRCTN66357938
- Lead Sponsor
- niversity College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Male
- Target Recruitment
- 4914
General inclusion criteria
1. At least 18 years old
2. Histological confirmation of prostate adenocarcinoma on a biopsy of the prostate or metastases, or a strong clinical suspicion of prostate cancer with consent from the patient and a plan to undergo a confirmatory tissue biopsy.
3. Confirmation of metastatic site(s) on CT or bone scan. Patients with metastatic disease meeting the following criteria are eligible:
• Metastatic disease to the bone (in any distribution) visible on 99Tc-Bone Scan
AND/OR
• Non-regional lymph node metastases of any size or distribution. Lymph nodes that are only visible on PET will not be eligible as sites of metastasis.
Note: If lymph nodes are the only site of metastases, then at least one must be at least 1.5cm in short axis AND outside of the pelvis
AND/OR
• Visceral metastases of any size or distribution
4. De novo presentation or, if relapsed, all hormonal treatments (ADT and ARSI) will have been completed =1 year prior to any future randomisation into any of the comparisons and have received =1 year total of ADT. This will be checked again at randomisation.
5. If not already started, there must be intention to start long-term androgen deprivation therapy (ADT).
6. WHO performance status 0-2 (For WHO performance status definitions see Appendix 1) or if WHO Performance Status 3, deemed to be due to metastatic burden and expected to improve with ADT.
7. Willing and able to comply with trial treatments.
8. Patient has signed informed consent form for registration into the STAMPEDE2 Trial platform.
Eligibility for Molecular Biomarker Testing
In addition to the general eligibility criteria patients need to meet the following criteria for biomarker testing:
1. If patient has already commenced ADT, check that if there is adequate time for the biomarker test to be returned in time for randomisation into Comparison N no more than 6 months after starting ADT.
2. Have not yet commenced ARSI. If this has already started, patients will not be eligible for Comparison N or prospective biomarker testing, but they can still be considered for Comparisons S and P.
3. Have a tumour block that is available for testing and transferring to the central UCL biomarker lab. The location details for this block will be needed at the block request stage. Where patients have a confirmed alteration in one of the genes in the biomarker panel using a local regulatory cleared biomarker test, this can be used to assess biomarker status.
4. There are no contraindications to niraparib, abiraterone acetate, prednisolone or apalutamide according to the reference safety information.
5. Patient has provided signed informed consent for use of tissue for testing (if central testing is required).
Eligibility criteria for comparison S testing SABR
Patients who meet the general eligibility criteria can be considered for the SABR comparison.
Recruiting sites will assess metastatic disease burden using conventional imaging (baseline Tc-99m bone scintigraphy and CT/MRI scans) to assess number of metastatic bone and non-regional lymph node foci, and presence of visceral metastases. Patients will be classified as either ‘SABR-eligible’ or ‘SABR-ineligible’ using the following definition.
Definition of SABR-eligible disease:
Patients will be classified as SABR-eligible if they meet all the following criteria:
• 1-5 metastatic lesions (including either bone and/or non-regional lymph node sites) using conventional imaging.
• Clinician determination tha
General exclusion criteria
1. Clinically and pathologically overt small cell carcinoma
2. Metastatic brain disease or leptomeningeal disease
3. Any active malignancies (i.e., progressing or requiring any treatment in the previous 36 months) other than prostate cancer (except non-muscle invasive bladder cancer; non-melanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence)
4. Any other medical condition that in the investigator's opinion means the participant is unfit or unsuitable for long-term ARSI or the trial treatments in the comparison for which they are being considered.
Exclusion criteria For comparison S testing SABR
1. Prior radical treatment to the prostate (e.g., radical surgery and/or radiotherapy).
2. Intracranial metastatic disease
3. Prior treatment to a metastatic site (e.g., radiotherapy, surgery or RFA)
4. Significant or progressive neurological deficit such that emergency (within 24 hours) surgery or radiation required (e.g., metastatic spinal cord compression, or impingement of the cord or any other clinical scenario whereby urgent radiotherapy to the spine is required)
5. Any condition or co-morbidities in the judgement of the clinician that precludes procedures required to facilitate radiotherapy delivery e.g.
5.1. Disease staging and follow-up
5.2. Radiotherapy planning procedures
6. Any condition or co-morbidities in the judgement of the clinician that precludes the safe delivery of radiotherapy to the prostate (+/- pelvic lymph nodes) and/or metastases e.g., inflammatory bowel disease, significant systemic connective tissue disorder, radiological evidence of idiopathic pulmonary fibrosis)
7. Active malignancy other than prostate cancer within the last 36 months
8. Contraindication to MRI (e.g., pacemakers, except MRI-compatible pacemakers)
Exclusion criteria For comparison P testing 177LU-PSMA-617
1. Prior treatment with any of the following:
1.1. Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223
1.2. PSMA-targeted radioligand therapy
2. Symptomatic cord compression, or clinical/radiological findings indicative of impending cord compression
3. Any condition that precludes raised arms position
4. Unmanageable bladder outflow obstruction or urinary incontinence. (Note: bladder outflow obstruction or urinary incontinence which is manageable and controlled with best available standard of care (incl. drainage, pads) is permitted)
Exclusion criteria For comparison N testing NIRAPARIB-AA+P
1. Prior treatment with a poly ADP ribose polymerase (PARP) inhibitor, radiopharmaceutical or any chemotherapy for prostate cancer other than docetaxel outside the STAMPEDE2 trial.
2. History of adrenal dysfunction.
3. History or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML).
4. Known allergies, hypersensitivity, or intolerance to the excipients of AA, or Nira-AA DAT (refer to the IBs for Nira-AA DAT and AA).
5. Current evidence of any medical condition that would make prednisolone use contraindicated.
6. Presence of sustained uncontrolled hypertension. At randomisation, sites will be asked to provide one blood pressure reading (systolic <160 mmHg and diastolic blood pressure reading <100 mmHg) recorded within the 8 weeks prior to randomisation.
7. Received an investigational intervention not related to the STAMPEDE2 trial (including investigational vaccines) or used an invasive investigational medical device within 30 days of randomisati
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method