Trial Title:
A Randomised Controlled Platform Trial Testing Treatments in Metastatic Hormone Sensitive Prostate Cancer
NCT ID:
NCT06320067
Condition:
Prostate Cancer Metastatic
Conditions: Official terms:
Prostatic Neoplasms
Ascorbic Acid
Prednisolone
Docetaxel
Abiraterone Acetate
Niraparib
Methyltestosterone
Estrogens, Conjugated (USP)
Androgens
Pluvicto
Conditions: Keywords:
Hormone sensitive metastatic prostate cancer
Niraparib
PARP inhibition
Apalutamide
Stereotactic ablative body radiotherapy (SABR)
PSMA-Lutetium
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Platform trial testing three research comparisons where patients are randomised either to
experimental treatments in Arms S, P and N or their corresponding SoC control Arms A and
A(N).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Stereotactic Ablative Body Radiotherapy (SABR)
Description:
SABR is a way of giving focused high-dose radiotherapy. SABR given with a dose
fractionation schedule of 30Gy in 3-5 fractions over 1-2 weeks to up to 5 metastatic
lesions in the bone and/or non-regional (extra-pelvic) lymph nodes.
Arm group label:
Arm S of SABR Comparison
Other name:
Stereotactic body radiotherapy (SBRT)
Intervention type:
Other
Intervention name:
177Lu-PSMA-617
Description:
177Lu-PSMA-617 is a nuclear medicine therapy. Patients will receive 177Lu-PSMA-617 to a
dose of 7.4GBq. Each cycle will consist of 2 doses, 1 week apart (on day 1 and day 8) and
will last 6 weeks. Treatment will be given for up to 3 cycles (6 doses).
Arm group label:
Arm P of 177Lu-PSMA-617 Comparison
Other name:
Lutetium (177Lu) Vipivotide Tetraxetan
Other name:
AAA617
Other name:
Pluvicto
Intervention type:
Drug
Intervention name:
Niraparib and Abiraterone Acetate Dual Action Tablet DAT
Description:
Combination product containing Niraparib (PARP inhibitor) and Abiraterone Acetate (ARSI).
The regular-strength dual-action tablet (DAT) contains 100 mg niraparib/500mg AA per
tablet. Patients take 2 tablets a day and receive a of total dose 200 mg niraparib/1000
mg AA. A low-strength DAT tablet containing 50 mg niraparib/500 mg AA may be available
for participants requiring a dose reduction of niraparib.
Arm group label:
Arm N of Niraparib Comparison
Other name:
Nira-AA
Other name:
CJNJ-67652000-ZZZ
Intervention type:
Drug
Intervention name:
Abiraterone Acetate
Description:
Abiraterone Acetate is an ARSI. Single agent Abiraterone Acetate may be used in patients
randomised to receive Niraparib and Abiraterone Acetate.
Arm group label:
Arm N of Niraparib Comparison
Other name:
Zytiga
Intervention type:
Drug
Intervention name:
Apalutamide
Description:
Apalutamide is an ARSI administered as a 240mg oral dose (four tablets taken together at
the same time every day) with or without food. It is given daily in 28-day cycles.
Arm group label:
Arm A(N) of Niraparib Comparison
Other name:
Erleada
Other name:
JNJ-56021927
Intervention type:
Drug
Intervention name:
Androgen Deprivation Therapy (ADT)
Description:
Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH
antagonists) if not previously surgically castrated. The choice of ADT is at the
discretion of the investigator. This will be given as standard of care as per local
guidelines.
Arm group label:
Arm A of 177Lu-PSMA-617 Comparison
Arm group label:
Arm A of SABR Comparison
Arm group label:
Arm A(N) of Niraparib Comparison
Arm group label:
Arm N of Niraparib Comparison
Arm group label:
Arm P of 177Lu-PSMA-617 Comparison
Arm group label:
Arm S of SABR Comparison
Intervention type:
Drug
Intervention name:
Androgen Receptor Signalling Inhibitor (ARSI)
Description:
Second generation ARSI (Abiraterone Acetate and Prednisolone [AA+P], Enzalutamide,
Apalutamide or Darolutamide). This will be given as standard of care as per local
guidelines.
Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to
be taken together once a day) with prednisolone 5mg once daily to prevent secondary
mineralocorticoid excess.
Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at
the same time every day) with or without food. Enzalutamide is administered daily in
28-day cycles.
Apalutamide will be administered as 240mg oral dose (four tablets taken together at the
same time every day) with or without food. Apalutamide is administered daily in 28-day
cycles. Patients require thyroid function monitoring.
Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together)
with or without food. Darolutamide is administered twice daily in 28-day cycles.
Arm group label:
Arm A of 177Lu-PSMA-617 Comparison
Arm group label:
Arm A of SABR Comparison
Arm group label:
Arm P of 177Lu-PSMA-617 Comparison
Arm group label:
Arm S of SABR Comparison
Intervention type:
Radiation
Intervention name:
Local Radiotherapy
Description:
Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions
over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20
fractions boost to involved nodes).
Arm group label:
Arm A of 177Lu-PSMA-617 Comparison
Arm group label:
Arm A of SABR Comparison
Arm group label:
Arm A(N) of Niraparib Comparison
Arm group label:
Arm N of Niraparib Comparison
Arm group label:
Arm P of 177Lu-PSMA-617 Comparison
Arm group label:
Arm S of SABR Comparison
Intervention type:
Drug
Intervention name:
Prednisolone
Description:
Prednisolone should also be administered 5mg daily using local pharmacy prescribing.
Arm group label:
Arm N of Niraparib Comparison
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.
Arm group label:
Arm A of 177Lu-PSMA-617 Comparison
Arm group label:
Arm A of SABR Comparison
Arm group label:
Arm A(N) of Niraparib Comparison
Arm group label:
Arm N of Niraparib Comparison
Arm group label:
Arm P of 177Lu-PSMA-617 Comparison
Arm group label:
Arm S of SABR Comparison
Summary:
STAMPEDE2 is a clinical trial comparing three new treatments with standard of care in
people with prostate cancer that has spread to other parts of the body and is responsive
to hormone therapy. People from all backgrounds and ethnicities are encouraged to take
part and multiple hospitals across the UK are involved. University College London is
running the trial.
Each comparison within the trial has its own control arm where people get the best
standard of care (Arm A) versus a research arm where a new treatment is added to standard
of care.
Participants are allocated to an arm by a computerised system with a 50% chance of
getting the research treatment.
Comparison S: Arm A versus Arm S (Stereotactic Ablative Body Radiotherapy (SABR)) - Tests
whether giving targeted doses of radiotherapy (SABR) to parts of the body where the
cancer has spread slows the spread of the cancer and improves survival. 2476 people will
be in this comparison.
Comparison P: Arm A versus Arm P (PSMA-Lutetium (177Lu-PSMA-617)) - Tests whether giving
a radioactive material (177Lu-PSMA-617) that targets prostate cancer cells slows the
spread of the cancer and improves survival. 1756 people will be in this comparison.
Comparison N: Arm A(N) versus Arm N (Niraparib-Abiraterone Acetate+Prednisolone
(Nira-AA+P)) - Tests whether giving a new drug (Nira-AA+P) slows the spread of the cancer
and improves survival. Only people with certain genetic changes in their tumour sample
can take part in Comparison N. 682 people will be in this comparison.
Participants may be able to take part in more than one comparison.
All participants will be followed up with scans and tests to monitor their cancer.
Doctors will check for any side effects from the treatments. Treatments will be stopped
if side effects are serious, or people no longer wish to take the treatments.
Criteria for eligibility:
Criteria:
4.4. ELIGIBILITY FOR REGISTRATION INTO THE STAMPEDE2 TRIAL
Inclusion criteria
I. At least 18 years old
II. Histological confirmation of prostate adenocarcinoma or a strong clinical suspicion
of prostate cancer with a plan to confirm the diagnosis formally before any future
randomisation.
III. Confirmation of metastatic site(s) on CT/MRI or bone scan. Patients with metastatic
disease meeting any of the following criteria are eligible:
- Metastatic disease to the bone (in any distribution) visible on 99Tc-Bone Scan
- 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.
- Visceral metastases of any size or distribution
IV. 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.
V. Long-term androgen deprivation therapy (ADT) has started or there is an intention to
start for a minimum of 2 years.
VI. WHO performance status 0-2 or if WHO Performance Status 3, deemed to be due to
metastatic burden and expected to improve with ADT. Note: Improvement to WHO status 0-2
will be checked again at randomisation into any subsequent comparison. Note: For WHO
performance status definitions see Appendix 1.
VII. Willing and able to comply with trial treatments.
VIII. Patient has signed informed consent form for registration into the STAMPEDE2 Trial
platform.
Exclusion criteria
I. Clinically and pathologically overt small cell carcinoma.
II. Metastatic brain disease or leptomeningeal disease.
III. 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).
IV. 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.
4.5. ELIGIBILITY FOR BIOMARKER TESTING FOR COMPARISON N
In addition to the general eligibility criteria in Section 4.4 participants need to meet
the following eligibility criteria for central biomarker testing for Comparison N:
Inclusion criteria
I. Confirm you have checked that there is adequate time for the central biomarker test
result to be returned so that randomisation into Comparison N would occur no more than 6
months after starting ADT.
II. Have a tumour block that is available for transferring to the Central Biomarker
Testing Laboratory. 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 accredited NHS biomarker test, this can be used to assess
biomarker status and if positive, the participant can proceed to eligibility assessment
for Comparison N. Permission to access the patient's tissue is still required for any
central confirmatory testing that might be required.
III. Patient has provided signed informed consent for use of tissue for testing.
Exclusion criteria
I. Patient has started ARSI therapy. If this has already started, patients will not be
eligible for Comparison N or central biomarker testing, but they can still be considered
for Comparisons S and P.
II. Contraindications to niraparib, abiraterone acetate, prednisolone or apalutamide
according to the reference safety information.
4.6. ELIGIBILITY CRITERIA FOR COMPARISON S TESTING SABR
Patients who meet the eligibility criteria in Section 4.4 can be considered for the SABR
comparison. Recruiting sites will assess metastatic disease burden using conventional
imaging (baseline Tc-99m bone scan 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 that metastatic lesions are considered suitable for SABR on
technical grounds (such as proximity of dose limiting normal tissue or tumour
volume).
- Absence of visceral metastases.
Otherwise, patients will be classified as SABR-ineligible.
In addition to the general registration eligibility criteria in Section 4.4, they need to
meet all the following criteria for entry into Comparison S:
Inclusion criteria
I. Patient still meets all eligibility criteria for registration in Section 4.4
II. Histological confirmation of prostate adenocarcinoma
III. Newly diagnosed (de novo) metastatic disease that is considered eligible for SABR
according to the definition in Section 4.6
IV. Patient has started ADT and randomisation is ≤12 weeks since the start of ADT
V. WHO performance status 0-2 (see Appendix 1)
VI. Patient has provided signed informed consent for participation in Comparison S
Exclusion criteria
I. Patient has relapsed prostate cancer
II. Prior radical treatment to the prostate (e.g., radical surgery and/or radiotherapy).
III. Intracranial metastatic disease.
IV. Prior treatment to a metastatic site (e.g., radiotherapy, surgery or RFA).
V. 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).
VI. Any condition or co-morbidities that, in the judgement of the clinician, preclude
procedures required to facilitate radiotherapy delivery e.g:
1. Disease staging and follow-up.
2. Radiotherapy planning procedures.
VII. Any condition or co-morbidities that, in the judgement of the clinician, preclude
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)
VIII. Active malignancy other than prostate cancer within the last 36 months.
4.7. ELIGIBILITY CRITERIA FOR COMPARISON P TESTING 177LU-PSMA-617
In addition to the general eligibility criteria in Section 4.4, patients need to meet the
following criteria for entry into Comparison P:
Inclusion criteria
I. Patient still meets all eligibility criteria for registration in Section 4.4.
II. Histological confirmation of prostate adenocarcinoma.
III. Patient meets the definition of SABR ineligible disease in Section 4.6.
IV. Patients must have adequate organ function as indicated by blood tests within 8 weeks
prior to randomisation:
Bone marrow function
1. ANC ≥1.5 x 109/L
2. Platelets ≥100 x 109/L
3. Haemoglobin ≥9g/dL, independent of transfusions for at least 28 days
Hepatic function
1. Total bilirubin ≤2 x ULN. For patients with Gilbert's Syndrome ≤3 x ULN is
permitted.
2. AST and/or ALT performed with all results ≤3 × ULN or ≤5 x ULN for patients with
liver metastasis
Renal Function
1. EGFR ≥50 mL/min/1.73m2 calculated using the MDRD formula
2. Albumin ≥25g/L
V. Patient has started ADT and randomisation is ≤12 weeks since start of current ADT.
VI. If relapsed, prior LHRH agonist/antagonist with or without first generation
anti-androgen use in the adjuvant/neo-adjuvant setting, hormone treatment must have been
discontinued >12 months prior to randomisation AND must not have exceeded 12 months of
therapy AND must not have shown disease progression within 12 months of completing
adjuvant/neo-adjuvant therapy.
VII. WHO performance status 0-2 (see Appendix 1).
VIII. Patient has provided signed informed consent for participation in Comparison P.
Exclusion criteria
I. Prior treatment with any of the following:
1. Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223
2. PSMA-targeted radioligand therapy
II. Symptomatic cord compression, or clinical/radiological findings indicative of
impending cord compression.
III. Any condition that precludes raised arms position.
IV. 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).
V. If taking part in the Imaging Substudy, contraindication to MRI (e.g., pacemakers,
except MRI compatible pacemakers).
4.8. ELIGIBILITY CRITERIA FOR COMPARISON N TESTING NIRAPARIB-AA+P
In addition to the general registration eligibility criteria in Section 4.4, patients
need to meet the following criteria for randomisation into Comparison N:
Inclusion criteria
I. Patient still meets all eligibility criteria for registration in Section 4.4 of master
protocol.
II. Histological confirmation of prostate adenocarcinoma.
III. Biomarker-positive status as defined in Section 9.4 of master protocol.
IV. Patients must have adequate organ function as indicated by blood tests within 8 weeks
prior to randomisation:
1. Absolute neutrophil count ≥1.5 x 109/L
2. Haemoglobin ≥9.0 g/dL, independent of transfusions for at least 28 days
3. Platelet count ≥100 x 109/μL
4. Serum albumin ≥30 g/L
5. Creatinine ≤2 x upper limit of normal (ULN)
6. Serum potassium ≥3.5 mmol/L
7. Serum total bilirubin ≤1.5× ULN or direct bilirubin ≤1 x ULN (Note: In patients with
Gilbert's syndrome where total bilirubin is >1.5 × ULN, direct bilirubin of ≤1.5 ×
ULN is permitted
V. AST and/or ALT performed with all results ≤3 × ULN
VI. Patient has commenced ADT, with a start date of less than 6 months prior to
randomisation into Comparison N.
VII. If relapsed disease, prior LHRH agonist/antagonist with or without first generation
anti-androgen use in the adjuvant/neo-adjuvant setting, hormone treatment must have been
discontinued >12 months prior to randomisation AND must not have exceeded 12 months of
therapy AND must not have shown disease progression within 12 months of completing
adjuvant/neo-adjuvant therapy.
VIII. Has not received prior docetaxel treatment for prostate cancer or meets ALL of the
following criteria:
1. Received ≤6 cycles of docetaxel therapy
2. Received the last dose of docetaxel ≥3 weeks prior to starting on IMP and ≤3 months
prior to randomisation
3. Maintained a response to docetaxel of stable disease or better, in the view of the
investigator based upon imaging and/or PSA, prior to randomisation
IX. WHO performance status 0-2 (see Appendix 1 for WHO performance criteria).
X. Able to swallow the trial treatment tablets whole (clinician determined).
XI. Patient has provided signed informed consent for participation in Comparison N.
Exclusion criteria
I. Prior treatment outside the STAMPEDE2 trial with a poly ADP ribose polymerase (PARP)
inhibitor, radiopharmaceutical or any chemotherapy for prostate cancer other than
docetaxel.
II. History of adrenal dysfunction.
III. History or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid
leukaemia (AML).
IV. Known allergies, hypersensitivity, or intolerance to the excipients of AA, or Nira-AA
DAT (refer to the IBs for Nira-AA DAT and AA).
V. Currently taking and planning to continue any medications that are contraindicated for
the trial IMPs of Apalutamide, Abiraterone Acetate or Niraparib as described in the
Comparison N appendix.
VI. Current evidence of any medical condition that would make prednisolone use
contraindicated.
VII. 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.
VIII. Received an investigational intervention not related to the STAMPEDE2 trial
(including investigational vaccines) or used an invasive investigational medical device
within 30 days prior to randomisation.
IX. Patient has commenced ARSI therapy (including abiraterone acetate and prednisolone,
enzalutamide, apalutamide or darolutamide).
X. Patients who have had any of the following ≤28 days prior to randomisation:
1. A transfusion (platelets or red blood cells);
2. Hematopoietic growth factors;
3. Surgery requiring general anaesthetic
XI. Known active hepatitis B virus (e.g., hepatitis B surface antigen reactive) or active
hepatitis C virus (HCV; e.g., HCV ribonucleic acid [RNA] [qualitative] is detected).
XII. Known HIV infection and any one of the following:
1. AIDS defining opportunistic infection within 6 months prior to randomisation
2. HAART or ART regimen non-compatible with the drugs of the study due to drug-drug
interaction with Niraparib (e.g., Protease inhibitors, cobicistat, efavirenz,
nevirapine, etravirine, doravirine and rilpivirine)
3. CD4 count below 300/mm3 within the 8 weeks prior to randomisation.
4. Detectable viral load within the 8 weeks prior to randomisation.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Royal Devon University Hospital Trust
Address:
City:
Exeter
Zip:
EX2 5DW
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
London
Zip:
NW3 2PG
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Royal Marsden Hospital
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Royal Marsden Hospital
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Start date:
June 11, 2024
Completion date:
March 2034
Lead sponsor:
Agency:
University College, London
Agency class:
Other
Collaborator:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
Novartis
Agency class:
Industry
Collaborator:
Agency:
Janssen Pharmaceutica NV
Agency class:
Other
Source:
University College, London
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06320067
http://www.stampede2trial.org
