Content - STAMPEDE

STAMPEDE - Systemic therapy for progressive or metastatic cancer of the prostate

STAMPEDE is an international, multi-arm, multi-phase, controlled and randomized trial on advanced carcinoma of the prostate. The main aim of the trial is to evaluate the safety and efficacy of new first-line treatments for patients starting hormonal therapy, in the case of advanced prostate carcinoma, using several medicines and radiotherapy in combination.

After responding to the initial treatment of hormonal suppression (either by medication or by orchiectomy), the cancer develops into a hormone-resistant carcinoma after about 1 to 2 years and then progresses. Patients could tolerate combination therapy at the start of hormonal suppression therapy better and the progression of the carcinoma could possibly be delayed. STAMPEDE is being conducted over 7 to 12 years in Switzerland and abroad. A total of 7000 patients will take part in this trial.

Study chair:

Prof. Dr. med. George Thalmann, Inselspital Bern, +41 31 632 36 64

  • Contacts at the hospitals

  • Inclusion criteria

    HIGH-RISK NEWLY DIAGNOSED NON-METASTATIC NODE-NEGATIVE DISEASE

    Both:

    At least two of:

    • Stage 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 sought in advance of consent, after discussion with MRC CTU)

    OR NEWLY DIAGNOSED METASTATIC OR NODE-POSITIVE DISEASE

    At least one of:

    • Stage Tany N+ M0

    • Stage Tany Nany M+

    OR PREVIOUSLY TREATED WITH RADICAL SURGERY AND/OR RADIOTHERAPY, NOW RELAPSING1

    At least one of:

    • PSA ≥4ng/ml and rising with doubling time less than 6 months

    • PSA ≥20ng/ml

    • N+

    • M+

    AND FOR ALL PATIENTS

    • Histologically confirmed prostate adenocarcinoma

    • Intention to treat with long-term androgen deprivation therapy

    • Fit for all protocol treatment2 and follow-up, WHO performance status 0-23

    • Have completed the appropriate investigations prior to randomisation

    • Adequate haematological function: neutrophil count >1.5x109/l and platelets >100x109/l

    • Estimated creatinine clearance >30ml/min

    • Serum potassium ≥3.5mmol/L

    • Written informed consent

    • Willing and expected to comply with follow-up schedule

    • Using effective contraceptive method if applicable

  • Exclusion criteria

    Patients must not fulfil any of the criteria, below.

    Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in Section 4.1.Metastatic brain disease or leptomeningeal disease 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 51.3μmol/l or 3mg/dl)

    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN

    • Any other previous or current malignant disease which, in the judgement of the responsible physician, is likely to interfere with STAMPEDE treatment or assessment

    • Patients with contra-indications to prednisolone, including active peptic ulceration or a history of gastrointestinal bleeding

    • Patients with active inflammatory bowel disease

    • Symptomatic peripheral neuropathy grade (NCI CTC)

    • Any surgery (e.g. TURP) performed within the past 4 weeks

    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:

    • 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 (NYHA II-IV)

    • Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 2 years prior to randomisation

    • Patients with uncontrolled hypertension defined as systolic BP greater or equal than 160 mmHg or diastolic BP greater or equal than 95 mmHg

    • Patients receiving treatment with drugs known to induce CYP3A4 (including phenytoin, carbamazepine, Phenobarbital)

    • Prior exposure to abiraterone

    • Prior exposure to enzalutamide

    • Prior chemotherapy for prostate cancer

    • Prior therapy with zoledronic acid or other bisphosphonates other than treatment for hypercalcaemia or low bone density

    • Prior exposure to policy of long-term hormone therapy before randomisation (unless as described in Section 4.4.2)

    • History of seizure including any febrile seizure, loss of consciousness, or transient ischaemic attack within 12 months of randomisation or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)

    • Unexplained history of loss of consciousness within 12 months of randomisation

    • Operation of heavy machinery during treatment

    SELECTION CRITERIA FOR COMPARISON OF RESEARCH (M1) RT FOR METASTATIC DISEASE

    All patients meeting criteria in Section 4.1 and 4.2 are eligible for the trial, but not all can be allocated to the research (M1) radiotherapy arm. The selection criteria for this "RT to the prostate" comparison are:

    • Newly-diagnosed prostate cancer

    • Demonstrable M1 disease

    • No contraindication to radiotherapy e.g. no previous pelvic radiotherapy and no history of inflammatory bowel disease

    • No previous radical prostatectomy Any patients meeting these criteria will have a chance to be allocated to Arm H.

Locations for this trial:

Hirslanden Klinik Aarau
Schänisweg
0 5001 Aarau
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Inselspital
Freiburgstrasse 8
3010 Bern
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Kantonsspital Liestal
Rheinstrasse 26
0 4410 Liestal
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Kantonsspital Winterthur
Brauerstrasse 15
0 8401 Winterthur
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich
Stadtspital Triemli
Birmensdorferstrasse 497
0 8063 Zürich
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Spitalzentrum Biel
Vogelsang 84
0 2501 Biel