MRC Clinical Trials Unit at UCL
90 High Holborn
Participants must fulfil both of the criteria in Section 1 or at least one criterion in Section 2 or at least one criterion in Section 3 of the protocol. Additionally, all patients must fulfil the criteria in Section 4.
Please note there is a typo within protocol version 17, where in one occasion it states that the pre hormone treatment PSA value must be attained within 8 months prior to randomisation, and in other locations within the protocol it states within 6 months. All pre hormone treatment PSA values must be within 6 months prior to randomisation.
1. High-Risk Newly-Diagnosed Non-Metastatic Node-Negative Disease
2. Newly-Diagnosed Metastatic Or Node-Positive Disease
At least one of:
3. Previously Radically Treated, Now Relapsing (Prior Radical Surgery And/or Radiotherapy)
At least one of
4. For All Patients
1. Histologically confirmed prostate adenocarcinoma
2. Intention to treat with long-term androgen deprivation therapy
3. Fit for all protocol treatment1 and follow‑up, WHO performance status 0-22
4. Have completed the appropriate investigations prior to randomisation
5. Adequate haematological function: neutrophil count >1.5x109/l and platelets >100x109/l
6. Adequate renal function, defined as GFR >30ml/min/1.73m2
7. Written informed consent
8. Using effective contraceptive method if applicable
Patients must not fulfil any of the criteria, below.
1. Prior systemic therapy for locally‑advanced or metastatic prostate cancer (except as listed in Section 4.33)
2. Prior exposure to hormone therapy for a duration of > 12 months, or prior exposure completing < 12 months before randomisation (see Section 4.3.1 for permitted prior exposure details)
3. Metastatic brain disease or leptomeningeal disease
4. Abnormal liver functions consisting of any of the following:
5. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment
6. Any surgical wound (e.g. TURP) which in the judgement of the responsible clinician may interfere with or be exacerbated by protocol treatment
7. Patients with significant cardiovascular disease including;
1 Medical contraindications to the trial medications are given in Section 6
2 For WHO performance status definitions see Appendix A
3 Details timelines for recently initiated SOC docetaxel, abiraterone, enzalutamide, apalutamide
In addition to the general inclusion and general exclusion criteria the following comparison-specific inclusion criteria must be met to be eligible for randomisation to the "metformin comparison":
The method used to determine glomerular filtration rate may vary according to local practice. Equations that either estimate glomerular filtration rate (eGFR) or creatinine clearance (CrCl) may be used and the same threshold value applies. Where possible, HbA1c should be performed prior to commencing SOC docetaxel to reduce the likelihood of corticosteroid-related hyperglycaemia impacting on eligibility. All participants with abnormal baseline HbA1c (i.e. 6.5% or higher) should be informed and referred to their GP for further management.
Eligibility for metformin metabolic sub-study
All newly randomised trial participants who meet the eligibility criteria to join the A/K comparison are eligible to join the metformin metabolic sub-study, if the site where they are being treated is participating in this sub-study. A limited number of sites will be recruiting for this sub-study. Selected sites involved have volunteered and demonstrated they have sufficient resources to undertake the metabolic sub-study.
Participants who are eligible for randomisation to the metformin comparison must be willing to take part in the metabolic sub-study and be able to adhere to the blood sample schedule. Appropriate consent to the additional blood samples must be provided.
In addition to the general inclusion and exclusion criteria, participants fulfilling all of the following are eligible for the “transdermal oestradiol comparison”:
Participant eligibility will be confirmed during the randomisation process and participants will be allocated to any of the open research comparisons for which they are eligible. To randomise a participant please carefully complete the Randomisation CRF and Eligibility Checklist and then contact the CTU.
Call the MRC CTU at UCL, Monday to Friday 0900-1700, excluding public holidays or dates when notice has been given by the CTU.
Tel: +44 (0) 20 76704777
N.B - While the CTU team are working remotely please email the STAMPEDE team (firstname.lastname@example.org) to request a randomisation, and we will call you back.
A trial ID and treatment will be allocated and given over the phone or by email. In addition, a letter confirming these details will be sent. The trial ID will be the primary way in which the participant will be identified and should be used in all correspondence. Centres should send a letter to the participant’s GP to inform them of their trial participation and treatment allocation. The GP letter is supplied as a template and can be downloaded from the trial website.
Interventional clinical trials
STAMPEDE participants should not join any other interventional clinical trials of prostate cancer treatment until the following criteria have been met:
Once both criteria are satisfied the participant may be entered into further treatment studies evaluating treatments for CRPC.
Site investigators should check with the CTU prior to participants commencing any IMP within an interventional clinical trial for any other medical condition, such as a new malignancy, to ensure there are no concerns about interactions with STAMPEDE treatments. Note that STAMPEDE treatment can be continued alongside non-trial treatments for a new malignancy providing local pharmacy review to ensure there are no interactions.
The primary outcome measure of STAMPEDE is overall survival, therefore follow‑up must continue after co-enrolment (unless the participant withdraws consent). Participation in interventional studies must be reported to CTU on the Co-enrolment CRF. Details of any interventional treatments received post-progression in such studies must be reported on the Additional Treatment Log.
Non-interventional clinical trials
Co-enrolment in non-interventional studies for any indication is permitted at any time providing that it does not interfere with treatment or assessment in STAMPEDE. This does not require reporting using the Co-enrolment CRF which captures details of interventional prostate cancer clinical trials only.
Data sharing agreements with “downstream” trials are encouraged to improve data quality in both trials and to reduce costs to both organisations.
MRC Clinical Trials Unit at UCL
90 High Holborn
Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy
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