Patient Eligibility

 
Inclusion Criteria

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

Both:

  • At least two of: T category T3/4, PSA≥40ng/ml or Gleason sum score 8-10
  • Intention to treat with radical radiotherapy (unless there is a contra-indication; exemption can be sought in advance of consent, after discussion with CTU)

 

OR

2. Newly-Diagnosed Metastatic Or Node-Positive Disease

At least one of:

  • Stage Tany N+ M0
  • Stage Tany Nany M+

 

OR

3. Previously Radically Treated, Now Relapsing (Prior Radical Surgery And/or Radiotherapy)

At least one of

  • PSA ≥4ng/ml and rising with doubling time less than 6 months
  • PSA ≥20ng/ml
  • N+
  • M+

 

AND

4. For All Patients

1. Histologically confirmed prostate adenocarcinoma

2. Intention to treat with long-term androgen deprivation therapy

3. Treating clinician and patient should have decided if additional systemic therapy with docetaxel or abiraterone is to be used as part of the standard-of-care prior to randomisation

4. Fit for all protocol treatment1 and follow-up, WHO performance status 0-22

5. Have completed the appropriate investigations prior to randomisation

6. Adequate haematological function: neutrophil count >1.5x109/l and platelets >100x109/l

7. Adequate renal function, defined as GFR >30ml/min/1.73m2

8. Written informed consent

9. Willing and expected to comply with follow-up schedule

10. Using effective contraceptive method if applicable

1 Medical contraindications to the trial medications are given in Section 6

2 For WHO performance status definitions see Appendix A

 

Exclusion Criteria

Patients must not fulfil any of the criteria, below.

1. Prior systemic therapy for locally-advanced or metastatic prostate cancer

2. Metastatic brain disease or leptomeningeal disease

3. Abnormal liver functions consisting of any of the following:

  • Serum bilirubin ≥1.5 x ULN (except for patients with Gilbert’s disease, for whom the upper limit of serum bilirubin is 51.3μmol/l or 3mg/dl)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN

4. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment

5. Any surgery (e.g. TURP) performed within the past 4 weeks

6. Patients with significant cardiovascular disease including;

  • Severe/unstable angina
  • Myocardial infarction less than 6 months prior to randomisation
  • Arterial thrombotic events less than 6 months prior to randomisation
  • Clinically significant cardiac failure requiring treatment, defined as New York Heart Association (NYHA) class II or above1
  • Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 6 months prior to randomisation
  • Or any other significant cardiovascular disease that in the investigator's opinion means the participant is unfit for any of the study treatments.

7. Prior chemotherapy for prostate cancer2

8. Prior exposure to long-term hormone therapy before randomisation

9. Prior exposure to systemic treatment for prostate cancer (excluding ADT or participants receiving abiraterone as part of SOC)

1 NYHA classifications can be found in Appendix A

2 Excluding participants receiving docetaxel as part of SOC

 

For Randomisation to the “Metformin Comparison”

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":

  • Hb A1c <48mmol/mol (equivalent to <6.5%)*
  • Adequate renal function, defined as GFR ≥45ml/min/1.73m2 (except for Switzerland 3)
  • No history of lactic acidosis or pre-disposing conditions
  • Not current or previous treatment with metformin
  • No contra-indications to metformin

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.

 

For Randomisation To The “Transdermal Oestradiol Comparison”

In addition to the general inclusion and exclusion criteria, participants fulfilling all of the following are eligible for the “transdermal oestradiol comparison”:

  • ≤8 weeks of anti-androgen (AR-antagonists) use
  • ≤1 dose of monthly or 4-weekly LHRH agonist/antagonist
  • No prior LHRH agonist injection with a stated duration of effect greater than 1 month
  • ≤12 weeks since first dose of any hormone therapy
  • Not had a bilateral orchidectomy
  • No use of cyproterone acetate (77) prior to randomisation
  • No known porphyria
  • No known history of deep vein thrombosis or pulmonary embolism confirmed radiologically
  • No known thrombophilic disorder (e.g. Protein C, Protein S, antithrombin deficiency)
  • Not planned to receive SOC abiraterone (see Section 4.3.4 for information)

 

Randomisation

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 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

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.

 

Co-Enrolment Guidelines

STAMPEDE participants should not join any other interventional clinical trials of prostate cancer treatment until a failure-free survival (FFS) event has been experienced and reported. After this point, the participant may be entered into further treatment studies e.g. evaluating treatments for CRPC. The primary outcome measure of STAMPEDE is overall survival and follow-up reports must continue after co-enrolment. Participation in post-progression studies must be reported to CTU on the Co-enrolment CRF; details of any interventional treatments received post-progression in such studies should be reported on the Additional Treatment Log.

Data sharing agreements with "downstream" trials are encouraged to improve data quality in both trials and to reduce costs to both organisations.

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 is designed to capture interventional prostate cancer clinical trials only.

 

 

STAMPEDE

Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy

See the latest News in STAMPEDE through the link to the right.