STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)
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|ClinicalTrials.gov Identifier: NCT00268476|
Recruitment Status : Recruiting
First Posted : December 22, 2005
Last Update Posted : September 25, 2017
|First Submitted Date ICMJE||December 20, 2005|
|First Posted Date ICMJE||December 22, 2005|
|Last Update Posted Date||September 25, 2017|
|Start Date ICMJE||September 2005|
|Estimated Primary Completion Date||September 2024 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Overall survival [ Time Frame: 1:Not applicable ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00268476 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial|
|Official Title ICMJE||STAMPEDE: Systemic Therapy in Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy - Androgen Suppression-Based Therapy Alone or Combined With Zoledronic Acid, Docetaxel, Prednisolone, Celecoxib, Abiraterone, Enzalutamide and/or Radiotherapy, Metformin and Transdermal Oestradiol in Treating Patients With Locally Advanced or Metastatic Prostate Cancer|
Prostate cancers need the male hormone testosterone to grow. Hormone treatments work by stopping testosterone from reaching prostate cancer cells. There are different types of hormone treatments but the most common are injections or implants that work by stopping the testicles making testosterone. Some men will have an operation to remove a part or all of the testicles instead. This type of treatment is called hormone treatment or androgen deprivation therapy (ADT) and it is part of the current standard approach to the treatment of locally advanced or metastatic prostate cancer. In addition, radiotherapy to the prostate and or docetaxel chemotherapy may be recommended as part of the current standard-of-care.
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 16.0 onwards (activated in June 2017) 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)
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.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Prostate Cancer|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||8100|
|Estimated Completion Date||September 2024|
|Estimated Primary Completion Date||September 2024 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
GENERAL INCLUSION CRITERIA
To be eligible participants must fulfil the criteria within one of the broad disease categories below:
In addition all patients must meet the following criteria:
I. Histologically confirmed prostate adenocarcinoma
II. Intention to treat with long-term androgen deprivation therapy
III. Treating clinician and patient should have decided if docetaxel is to be part of the standard-of-care prior to randomisation
IV. Fit for all protocol treatment and follow-up, WHO performance status 0-2
V. Have completed the appropriate investigations prior to randomisation
VI. Adequate haematological function: neutrophil count >1.5x109 /l and platelets >100x109 /l
VII. Adequate renal function, defined as GFR >30ml/min/1.73m 2
VIII. Serum potassium ≥3.5mmol/L
IX. Written informed consent
X. Willing and expected to comply with follow-up schedule
XI. Using effective contraceptive method if applicable
Patients must not fulfil any of the following general exclusion criteria
I. Prior systemic therapy for locally-advanced or metastatic prostate cancer (except previously radically treated, now relapsing patients (prior radical surgery and/ or radiotherapy)
II. Metastatic brain disease or leptomeningeal disease
III. Abnormal liver functions consisting of any of the following:
IV. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment
V. Any surgery (e.g. TURP) performed within the past 4 weeks
VI. Patients with significant cardiovascular disease such that, in the investigator's opinion, the patient is unfit for any of the study treatments. This might include:
VII. Prior chemotherapy for prostate cancer (excluding patients receiving docetaxel as part of the new SOC)
VIII. Prior exposure to long-term hormone therapy before randomisation. (Any patients now presenting with relapsed disease, previously treated with adjuvant or neo adjuvant hormone therapy alongside their radical surgery or radiotherapy, must have completed that period of hormone therapy at least 12 months before joining STAMPEDE and it must have been no longer than 12 months in duration).
IX. Prior exposure to systemic treatment for prostate cancer (excluding hormone therapy) e.g. abiraterone and enzalutamide.
Comparison-Specific Selection Criteria
To be eligible for randomisation to the "metformin comparison" patients must fulfil the following criteria:
Patients who have any of the following are not eligible for the "transdermal oestradiol comparison":
|Ages||up to 120 Years (Child, Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||Switzerland, United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT00268476|
|Other Study ID Numbers ICMJE||CDR0000455008
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Medical Research Council|
|Study Sponsor ICMJE||Medical Research Council|
|Collaborators ICMJE||Not Provided|
|PRS Account||Medical Research Council|
|Verification Date||September 2017|
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