Last updated on November 2018

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


Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: Malignant neoplasm of prostate
  • Age: - 120 Years
  • Gender: Male

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.

  1. High-Risk Newly-Diagnosed Non-Metastatic Node-Negative Disease
    Both
    • At least two of: T category T3/4, PSA40ng/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 docetaxel is to be 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
  11. Medical contraindications to the trial medications are given in Section 6
  12. 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 except as listed above
  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 51.3mol/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. Participant 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":

HbA1c <48mmol/mol (equivalent to <6.5%)*

Adequate renal function, defined as GFR 45ml/min/1.73m2

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

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


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