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

Phase 1

• Conditions: Prostate Cancer; MedDRA version: 20.0Level: LLTClassification code 10001186Term: Adenocarcinoma of prostateSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10001198Term: Adenocarcinoma of the prostate metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10001199Term: Adenocarcinoma of the prostate recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10007113Term: Cancer of prostateSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10007453Term: Carcinoma of the prostate metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10007454Term: Carcinoma of the prostate recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10007462Term: Carcinoma prostateSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps

• Registration Number: EUCTR2004-000193-31-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-08-21
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 12000

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, 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 T-any N+ M0
• Stage T-any N-any 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

I.Histologically confirmed prostate adenocarcinoma
II.Intention to treat with long-term androgen deprivation therapy
III.Fit for all protocol treatment(1) and follow up, WHO performance status 0-2 (2)
IV.Have completed the appropriate investigations prior to randomisation
V.Adequate haematological function: neutrophil count =1.5x109/l and platelets =100x109/l
VI.Adequate renal function, defined as GFR =30ml/min/1.73m2
VII.Written informed consent
VIII.Willing and expected to comply with follow up schedule
IX.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

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 )
•No history of lactic acidosis or predisposing conditions
•No current or previous treatment with metformin
•No current or previous medication for treatment of diabetes
•No contraindications to metformin
•Willingness to join the metabolic sub study

*Except Switzerland, please refer to SAKK appendix for local guidance

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
•Maximum of 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 (36) 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 yet started SOC abiraterone, enzalutamide or apalutamide

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5800

Exclusion Criteria

I.Prior systemic therapy for locally advanced or metastatic prostate cancer (except as listed in Section 4.3)
II.Prior exposure to hormone therapy for a duration of > 12 months, or prior exposure completing < 12 months before randomisation
III.Metastatic brain disease or leptomeningeal disease
IV.Abnormal liver functions consisting of any of the following:
• Serum bilirubin =1.5 x ULN (except for participants 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 - site must indicate at randomisation whether one or both tests are performed at site. Where both results are available both must confirm eligibility.
V.Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment
VI.Any surgical wound (e.g. TURP) which in the judgement of the responsible clinician may interfere with or be exacerbated by protocol treatment
VII.Participants 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 above
•Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 6 months prior to randomisation
•Any other significant cardiovascular disease that in the investigator's opinion means the participant is unfit for any of the study treatments.

(1) Excluding participants receiving docetaxel as part of SOC

(2) NYHA classifications can be found in Appendix A

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified