Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy
- Conditions
- Prostate Cancer
- Interventions
- Drug: Transdermal OestradiolRadiation: Radiotherapy to the prostate
- Registration Number
- NCT00268476
- Lead Sponsor
- Medical Research Council
- Brief Summary
The overall aim of this trial, which is called STAMPEDE, is to assess novel approaches for the treatment of men with prostate cancer who are starting long-term ADT for the first time, termed hormone-naïve prostate cancer. This trial aims to see if we can improve the way in which prostate cancer is currently managed, either by adding new treatments to the standard approach or by modifying the type of hormone therapy aiming to improve quality-of-life by reducing the side effects of treatment. Each new treatment approach is compared against a control arm receiving the current standard treatments. We aim to identify treatment strategies that enable men to live longer, or as long but with an improved quality-of-life, as well as offering value for money for the health service.
Since opening to accrual in Oct-2005, the trial has tested many ways of treating prostate cancer and some results are now already known. More than 10,000 men will join the trial with answers becoming available throughout the trial. New patients joining the trial from Protocol version 17.0 onwards (activated in December 2018) may be eligible to join one of two treatment comparisons, metformin (treatment group K; the "metformin comparison") and transdermal oestradiol (treatment group L; the "transdermal oestradiol comparison"). A computer program will be used to allocate which treatment each participant receives, using a chance process.
Summary of the research arms in STAMPEDE trial platform Summary of research treatment groups currently open to recruitment (June 2017)
1. Metformin (Arm K): This anti-diabetic medication is proposed to have both anti-cancer effects and may help prevent the adverse metabolic effects of long-term ADT. STAMPEDE will investigate whether adding metformin to the current standard-of-care for non-diabetic men can improve all-cause survival.
2. Transdermal oestradiol (Arm L): This is an alternative form of hormone treatment which has been shown to suppress testosterone as effectively as standard ADT and avoid some of the side-effects. It may also help to avoid the adverse metabolic effects and fatigue and therefore improve overall quality of life compared with standard forms of ADT. STAMPEDE will investigate whether transdermal oestradiol can treat the cancer as well as current standard forms of ADT.
3. Control group (Arm A): Patients allocated to this group receive the current standard-of-care ADT +/- RT +/- docetaxel.
- Detailed Description
STAMPEDE (also known as MRC PR08) is a multi-arm multi-stage (MAMS) randomised controlled trial recruiting in the UK and Switzerland. It aims to evaluate multiple therapeutic strategies in the management of high-risk locally advanced and metastatic hormone-naïve prostate cancer. Each novel treatment strategy is compared against a single, contemporaneous control arm. When the trial originally opened in 2005 there were 6 research arms enabling 5 randomised comparisons. Each comparison is evaluated in stages with pre-planned interim analyses after which recruitment may be halted should the experimental treatment fail to reach a "hurdle" of activity. Patient data from all arms and all stages are, however, included in the final analyses of the primary outcome measure, even if the investigational arm did not proceed to the final stage.
Providing sufficient activity is demonstrated, recruitment continues to the final stage and then an assessment of efficacy is determined based on the primary outcome of overall survival. Patient data from all arms and all stages are included in the final analyses of the primary outcome measure, even if the investigational arm did not proceed to the final stage.
The original comparisons which have all now been reported, evaluated a bisphosphonate (zoledronic acid), a cytotoxic chemotherapeutic agent (docetaxel) and a cyclooxygenase (Cox 2) inhibitor (celecoxib), as single agents or combinations. Since the start of the trial, a number of new research arms have been added to STAMPEDE over time to evaluate: abiraterone, a steroid synthesis inhibitor; prostate radiotherapy for patients with newly diagnosed metastatic disease; enzalutamide, an inhibitor of androgen receptor signalling, given with abiraterone; and metformin, an anti-diabetic medication and transdermal oestradiol, to be given as an alternative form of ADT.
Objectives:
Primary
To compare the safety and efficacy of novel therapeutic strategies against the current standard-of-care for men with high-risk locally advanced or metastatic prostate cancer starting long-term ADT for the first time.
Outline: This is a randomised, controlled, multi-centre MAMS trial platform. Patients are current randomised to 1 of 3 arms: control group (arm A), metformin treatment group (arm K) and transdermal oestradiol (Arm L). The other arms are all closed to recruitment with results known for all the original comparisons and awaited for others added since the trial commenced.
Patient population: STAMPEDE recruits both men with high-risk locally advanced prostate cancer and men with metastatic prostate cancer, all of whom must be starting long-term ADT for the first time. Patients who received previous radical treatment and are now relapsing with high-risk features are also eligible.
Follow-up: All patients are follow-up life long
Sub-studies: There are several translational sub-studies ongoing as part of STAMPEDE. Participation is optional. These currently include several translational sub-studies involving sample collection: saliva collection for germline DNA analysis, sequential circulating tumour DNA analysis and FFPE tumour block retrieval for DNA and RNA analysis. Other sub-studies include a QOL sub-study and an imaging sub-study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 11992
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm G: Abiraterone ADT (ADT + abiraterone acetate + prednisolone) NO LONGER RECRUITING Arm K: Metformin ADT (ADT + Metformin) RECRUITING IN SELECTED SITES Arm C: Docetaxel ADT (ADT + docetaxel + prednisolone) NO LONGER RECRUITING Arm D: Celecoxib ADT (ADT + celecoxib) NO LONGER RECRUITING Arm L: tE2 Transdermal Oestradiol (Transdermal oestradiol) RECRUITING Arm G: Abiraterone Prednisolone (ADT + abiraterone acetate + prednisolone) NO LONGER RECRUITING Arm G: Abiraterone Abiraterone (ADT + abiraterone acetate + prednisolone) NO LONGER RECRUITING Arm C: Docetaxel Prednisolone (ADT + docetaxel + prednisolone) NO LONGER RECRUITING Arm D: Celecoxib Celecoxib (ADT + celecoxib) NO LONGER RECRUITING Arm A: Standard of Care ADT Androgen Deprivation Therapy \[ADT\] (plus Radiotherapy for newly-diagnosed non-metastatic disease, plus or minus Docetaxel, plus or minus Abiraterone)\[Control\] Arm B: Zoledronic Acid ADT (ADT + zoledronic acid) NO LONGER RECRUITING Arm J: Abiraterone * Enzalutamide Enzalutamide (ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING Arm E: Zoledronic Acid & Docetaxel ADT (ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING Arm F: Zoledronic Acid & Celecoxib ADT (ADT + zoledronic acid + celecoxib) NO LONGER RECRUITING Arm H: M1 RT Radiotherapy to the prostate (ADT + radiotherapy to the prostate) NO LONGER RECRUITING Arm H: M1 RT ADT (ADT + radiotherapy to the prostate) NO LONGER RECRUITING Arm J: Abiraterone * Enzalutamide ADT (ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING Arm B: Zoledronic Acid Zoledronic Acid (ADT + zoledronic acid) NO LONGER RECRUITING Arm C: Docetaxel Docetaxel (ADT + docetaxel + prednisolone) NO LONGER RECRUITING Arm E: Zoledronic Acid & Docetaxel Docetaxel (ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING Arm E: Zoledronic Acid & Docetaxel Prednisolone (ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING Arm E: Zoledronic Acid & Docetaxel Zoledronic Acid (ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING Arm F: Zoledronic Acid & Celecoxib Celecoxib (ADT + zoledronic acid + celecoxib) NO LONGER RECRUITING Arm K: Metformin Metformin (ADT + Metformin) RECRUITING IN SELECTED SITES Arm F: Zoledronic Acid & Celecoxib Zoledronic Acid (ADT + zoledronic acid + celecoxib) NO LONGER RECRUITING Arm J: Abiraterone * Enzalutamide Prednisolone (ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING Arm J: Abiraterone * Enzalutamide Abiraterone (ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING
- Primary Outcome Measures
Name Time Method Overall survival 1:Not applicable Time to mortality
- Secondary Outcome Measures
Name Time Method Skeletal related events 1:Not applicable Reporting the incidence and types of skeletal related events
Biochemical failure 1:Not applicable For the purposes of the STAMPEDE trial, a unique threshold PSA value for biochemical failure is calculated for each patient, referred to as the PSA progression value.
A. If PSA nadir in the 24 weeks following randomisation is more than 4ng/ml and more than 50% of the pre-treatment PSA level - immediate treatment failure.
B. If PSA nadir in the 24 weeks following randomisation is less than or equal to 50% of the pre-treatment PSA level but remains above 4ng/ml - treatment failure will be defined as a rise of 50% above the nadir level.
C. If PSA nadir in the 24 weeks following randomisation is less than or equal to 4ng/ml - treatment failure will be defined as at least 50% rise above the nadir value and also above 4ng/ml.Progression-free survival 1:Not applicable Reporting the incidence of mortality without a progression event
Lymph node progression 1:Not applicable Reporting the incidence and severity of lymph node events
Distant metastases 1:Not applicable Reporting the incidence and severity of distant metastatic events
Treatment for progression 1:Not applicable Identifying and reporting the treatments used in second line treatment. Incidence and types of treatments.
Disease-specific survival 1:Not applicable Reporting the mortality attributed to Prostate Cancer
Non-prostate cancer death 1:Not applicable Reporting the mortality not attributed to Prostate Cancer
Metabolic effects 1:Not applicable Reporting the incidence and severity of effects on metabolic systems
Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item 1:Not applicable Determination of changes in quality of life with interventions
Number of participants with treatment-related side effects as assessed by CTCAE v4.0 1:Not applicable Reporting the incidence, type and severity of side effects within the trial population. CTCAE v4.0 will be used to classify the events names and severity.
Cost effectiveness by EuroQol 1:Not applicable Reporting the comparison of costs associated with the additional treatments provided and the survival gain attributed to the additional treatments, to SOC alone.
Failure-free survival 1:Not applicable Report of time from initiation of treatment to the first progression event of each patient
Trial Locations
- Locations (118)
Kantonsspital Graubuenden
🇨🇭Chur, Graubunden, Switzerland
Lausanne Centre Hospitalier Universitaire
🇨🇭Lausanne, Vaud, Switzerland
Winterthur Hospital
🇨🇭Winterthur, Zurich, Switzerland
Hirslanden Klinik Aarau
🇨🇭Aarau, Switzerland
Universitaetsspital-Basel
🇨🇭Basel, Switzerland
Inselspital Bern
🇨🇭Berne, Switzerland
Liestal Hospital
🇨🇭Liestal, Switzerland
Kantonsspital - St. Gallen
🇨🇭St. Gallen, Switzerland
UniversitaetsSpital Zuerich
🇨🇭Zurich, Switzerland
City Hospital Triemli
🇨🇭Zurich, Switzerland
Scroll for more (108 remaining)Kantonsspital Graubuenden🇨🇭Chur, Graubunden, Switzerland