1. Tom Fairfield STAMPEDE Trial Manager
STAMPEDE Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy
Tom Fairfield
STAMPEDE Trial Manager
Sponsor number: MRC PR08 ISRCTN number: ISRCTN EUDRACT number: CTA number: /0026/

2. TRIAL DESIGN

3. Design rationale
STAMPEDE is 6-arm, 5-stage randomised controlled trial
3 investigational drugs
Using Multi-Arm Multi-Stage methodology
MAMS design
MAMS design permits rapid comparison and concurrent testing of treatments

4. Trial Design

5. Trial Design Stages Stage Outcome Measures Primary Secondary
Pilot Safety Feasibility
Activity I-III Failure-free survival Overall survival
Toxicity
Skeletal-related events
Efficacy IV Overall survival Failure-free survival
Quality of life

6. PATIENT SELECTION CRITERIA

7. Main Inclusion Criteria
Newly diagnosed high risk patients with one of
Any 2 out of the following 3
Stage T3/4 N0 M0
PSA  40ng/ml
Gleason sum score 8-10
Stage Tany N+ M0 or Tany Nany M+
Multiple sclerotic bone metastases with a PSA  100ng/ml
Previously treated relapsing patients with either
PSA  4ng/ml and rising with doubling time less than 6 months
PSA  20ng/ml N+ M+

8. Inclusion/Exclusion Criteria
Intention to treat with long term HT
WHO PS 0,1 or 2
Adequate cardiovascular history
No major dental extractions planned within next 2 years

9. Hormone Therapy Before Randomisation
It is preferable that patients are not started on hormones prior to randomisation
No more than 12 weeks before
PSA measurement taken before HT treatment

10. Screening Procedures Patients identifed
CT or MRI of pelvis and abdomen
Bone Scan
Chest X-ray and ECG
PSA Test
Within 8 Weeks of Randomisation
Blood Tests

11. TREATMENT ADMINISTRATION

12. Hormone Therapy Three acceptable approaches: Bilateral orchidectomy
Total or subcapsular
LHRH analogues
Used according to local practice
Prophylactic anti-androgens recommended
Anti-Androgens
M0 patients only
Monotherapy according to local practice

13. Zoledronic acid Zoledronic acid 4mg 15min IV infusion
Every 3 weeks for 6 treatments
Then every 4 weeks
Patients should also receive
500mg calcium oral supplement
400IU vitamin D oral supplement
Available as a combination tablet
Continues until the soonest of:
Maximum of 2 years
disease (including PSA) progression

14. Docetaxel Docetaxel 75mg/m2 Patients should also receive Continues:
Day 1 as 1hr IV infusion
Max 160mg
Patients should also receive
Prednisolone 5mg bid daily for 21 days
Continues:
Cycle repeated every 3 weeks for 6 cycles

15. Celecoxib Celecoxib 400mg Continues until the soonest of: bid
Maximum of 1 year
Disease (including PSA) progression

16. Radiotherapy Radiotherapy permitted for suitable patients
Intention to use RT stated at randomisation
ensure no bias towards particular combinations of systemic therapy with radiotherapy
RT given 6 to 9 months after randomisation
and after any docetaxel toxicity settled

17. ASSESSMENTS & FOLLOW-UP

18. Follow-up schedule 6 weekly 0 to 24 weeks 12 weekly up to 2 years
6 monthly up to 5 years
Annually thereafter

19. Assessment of Treatment Failure
New lesions
CT scan
Increase in baseline lesions
Biochemical
Rate of fall of PSA and the level of the PSA nadir
PSA nadir will be sent to responsible clinician confirming the PSA level which would be taken as progression.
Death from prostate cancer

20. Defining PSA Nadir & PSA Failure
Lowest reported PSA level
Between randomisation and 24 weeks
PSA Failure
Depends on baseline PSA measurement and PSA nadir
3 possible PSA failure categories, A, B and C

21. PSA Failure Categories

22. Defining PSA Relapse For patients in group A – Failed at time zero
For Patients in group B – Relapse occurs when PSA increases by 50% above nadir
For Patients in group C – Relapse occurs when PSA increases by 50% above nadir or goes above 4ng/ml, whichever is greatest

23. DRUG SUPPLY

24. Drug Supply & Support Novartis Pfizer Sanofi-Aventis
Supplying free Zoledronic Acid
Providing an educational grant to support some central work
Pfizer
Supplying free Celecoxib
Providing funds to distribute drug to centres
Sanofi-Aventis
Providing an educational grant
Supplying Docetaxel at a discounted price of buy 1 get 2 free

25. Drug Supply & Support Department of Health Central subvention provided
£1,787 per patient randomised to arms C and E of the trial and prescribed docetaxel.
Payable in respect of a hospital trust randomising more than 3 patients

26. Drug Ordering and Labelled
Celecoxib and Zoledronic Acid
Ordered by MRC CTU at accreditation and on subsequent request from centres
Docetaxel
Ordered by centre pharmacist
All drugs
To be labelled by the pharmacist using labels provided

27. CURRENT ACCRUAL

28. Current Recruitment Status
First patient
17th October 2005
Accrual targets
Pilot Phase target was 210 patients
Pilot Phase target achieved in March 2007
Overall target approximately 3300 patients
(440 OS events on control arm)
Observed accrual
2114 patients have been randomised
28th February 2011

29. Accrual

30. Patient Characteristics
Age (years) at randomisation median (quartiles)
65 (60-70)
PSA (ng/ml) at randomisation median (quartiles)
66 (23-183)
WHO performance status (0 Vs 1 Vs 2+)
1628 vs 460 vs 25
Bone mets at randomisation n (%)
1080 (51%)
RT planned n (%)
521 (25%)
Type of HT: (LHRH vs bicalutamide vs orchidectomy)
2069 vs 35 vs 10
High risk newly diagnosed pts n (%)
1975 (93%)
Previously treated/relapsing pts n (%)
139 (7%)
Data from 28th Feb 2011

31. TRIAL COMMITTEES AND CONTACTS

32. Trial Management Group
Nick James Oncologist; CI, Chair, Birmingham, UK
Noel Clarke Urologist; Vice-Chair Manchester, UK
Malcolm Mason Oncologist; Vice-Chair Cardiff, UK
John Anderson Urologist Sheffield, UK
David Dearnaley Oncologist Sutton, UK
John Dwyer Patient representative Stockport, UK
John Masters Pathologist London, UK
Martin Russell Oncologist Glasgow, UK
Marc Schulper Health Economist York, UK
Andrew Stanley Pharmacist Birmingham, UK
George Thalmann Oncologist Bern, CH
Charlene Green Data Manager MRC CTU, UK
Gordana Jovic Statistician MRC CTU, UK
Erika Kuettel Trial Coordinator SAKK, CH
Max Parmar Statistician MRC CTU, UK
Tom Fairfield Trial Manager MRC CTU, UK
Matthew Sydes CTU Lead/Trial Statistician MRC CTU, UK

33. Contact us Tom Fairfield Trial Manager MRC Clinical Trials UnitE:
Charlene Green
Data Manager T: