Current trials in prostate cancer MalcolmMason

Current Trials in Prostate Cancer Malcolm Mason Prostate Cancer Research comes of age? Aetiology/prevention studies  Diagnosis/screening/early disease studies  Treatment of relapsed disease  Treatment of advanced disease/new systemic agents  Prostate Cancer Research comes of age?   Aetiology/prevention studies:  Familial studies (RMH) Diagnosis/screening/early disease studies   ProtecT CHHIP RADICALS Patch Stampede Phase IIs   Treatment of relapsed disease     Treatment of advanced disease/new systemic agents Prostate Cancer Research comes of age?   Aetiology/prevention studies:  Familial studies (RMH) (US !!) Diagnosis/screening/early disease studies   ProtecT US !! CHHIP (US !!) RADICALS US !! Patch (US !!) Stampede US !! Phase IIs US !!   Treatment of relapsed disease     Treatment of advanced disease/new systemic agents The Current UK Trials Portfolio Acronym Cardiovascular Prostate Study Title PI(s) Status Closed CHHIP CV247 DA v DAS in prostate cancer EORTC 22991 EORTC 30985 Familial prostate cancer study High Dose Rhenium Intercontinental An open study of cardiovascular and osteoporotic risk Mr Howard G factors in patients undergoing androgen deprivation Kynaston, therapy for prostate cancer Professor Malcolm Mason Conventional or Hypofractionated High Dose Intensity Dr David Modulated Radiotherapy for Prostate Cancer Dearnaley A randomised double-blind local phase III study of Dr Robert Thomas CV247 vs salicyclic acid in early prostate cancer A Randomised Phase II Trial of Dexamethasone and Dr Jonathan Aspirin (DA)Versus Dexamethasone, Diethylstilbestrol Shamash and Aspirin (DAS) in Locally Advanced or Metastatic Cancer of the Prostate Three Dimensional Conformal Radiotherapy alone Professor Malcolm versus Three Dimensional Conformal Radiotherapy Mason plus adjuvant hormonal therapy in localized T1b-c, T2a, N0, M0 prostatic carcinoma. A phase III randomized study. Intermittent androgen deprivation in patients with Dr David stage D2 prostate cancer-Phase III Dearnaley Familial Prostate Cancer: Epidemiology and Molecular Dr Ros Eeles Studies. The Cancer Research UK/British Prostate Group UK Familial Prostate Cancer Study High Activity Rhenium-186 HEDP with peripheral Dr David blood stem cell support in patients with bony Dearnaley, Dr Joe metastases in prostate cancer. O`Sullivan INTERmittent or CONTINuos ENdocrine Therapy Dr David After failure in Localised prostate cancer Dearnaley Open Open Open Open Open Open Closed Open MAPS PATCH PCSS PR07 Conservative treatment for urinary incontinence in Men After Prostate Surgery (MAPS): multicentre randomised controlled trial of pelvic floor muscle training, biofeedback and bladder training A randomised controlled trial of Transcutaneous Oestogen Patches versus LHRH analogues in prostate cancer The Prostate Cancer Symptoms Study Dr Cathryn Glazener Open Mt Paul Abel In set-up Process Prostate & Cognition Prostate HDR brachytherapy boost trial ProtecT RT01 SPIRIT STAMPEDE TAPS A randomised trial of hormone therapy plus radical radiotherapy versus hormone therapy alone in nonmetastatic prostate cancer Prostate Cancer in Ethnic Subgroups: A comparative Mr Biral Patel Closed study of Incidence, Clinical Presentation and access to Health Care in the UK (Process) An exploratory pilot study to investigate whether Dr Val Jenkins Closed hormonal therapy for prostate cancer has an adverse effect on cognition Randomised trial of interstitial brachythearpy as a Dr Peter Hoskin Closed component of radical radiotherapy for localised prostatic cancer The ProtecT Trial - Evaluating the effectiveness of Professor Jenny Open treatment for clinically localised prostate cancer Donovan, Professor Freddie Hamdy, Professor David E Neal A randomised trial of high dose therapy in localised Dr David Closed cancer of the prostate using Conformal radiotherapy Dearnaley techniques A Randomized Trial of Radical Prostatectomy versus Dr David Closed Brachytherapy for Patients with T1c or T2a N0 M0 Bottomley, Paul Prostate Cancer Lange Systemic Therapy in Advancing or Metastatic Prostate Professor Nicholas in set-up Cancer: Evaluation of Drug Efficacy James Targeted PSA screening for familial prostate cancer Dr Jane Melia Open Mr Stephen Open Langley Professor Malcolm Closed Mason PATCH Hypothesis Oestrogen administered in a way that avoids first pass hepatic metabolism could be an effective therapy for prostate cancer without the high incidence of CVS toxicity Trial Design Diagnosis Locally advanced, metastatic or relapsing prostate cancer about to start androgen deprivation therapy Randomise 2:1 Transcutaneous Oestrogen Patches LHRH analogues The ProtecT study 233,000 Invitations Men 50-69 years (Prostate testing for cancer and Treatment) 116,500 (50%) attendees Prostate check clinic 12,815 (11%) Raised PSA 2,050 (16%) Localised Advanced cancer Randomisation min 60% Active Monitoring 410-683 Radical Prostatectomy 410-683 Radical Radiotherapy 410-683 Preference 0-830 Annual research follow-up Acceptance of allocation by arm Randomised Overall Active monitoring Surgery 825 272 Accepted allocation 642 (78%) 240 (88%) Surgery 17 RadioT 9 Brachy 3 Ac Mon 45 RadioT 17 Brachy 4 Ac Mon 36 Surgery 21 Brachy 4 Changed to 263 192 (73%) Radiotherapy 266 199 (75%) ProtecT study – RT meeting update STAMPEDE Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy STAMPEDE Trial Design A Androgen suppression (AS): according to local practice Control arm R A N D O M I S E F AS + zoledronic acid + celecoxib: as above D AS + Celecoxib: 400mg bid until the sooner of 1 year or disease progression (including PSA) C AS + Docetaxel: 75mg/m 2 day 1 plus prednisolone 5mg bid continuously, every 3 weeks for 6 cycles B AS + Zoledronic acid: 4mg 3 weekly for 6 cycles and then 4mg 4 weekly for 2 years or until disease progression E AS + zoledronic acid + docetaxel: as above AS = Androgen suppression as in Arm A STAMPEDE In Development: RADICALS Radical prostatectomy Time Assess need for RT Immediate RT group Immediate RT Immediately after surgery Uncertain group RANDOMISE Immediately after surgery Deferred RT group RANDOMISE Monitor until rising PSA RT + no AD RT + short AD RT + long AD Trial follow-up Deferred RT RANDOMISE At rising PSA RT + no AD RT + short AD Trial follow-up Outcome measures Time Other highlights Forthcoming – CHHIP 3rd stage Awaited – Results of MRC PR07/ NCIC PR3 Novel agents New chemotherapeutic agents – Epothilones New biologicals – Growth factor/STIs – Antagonists of anti-apoptotic agents – HDAC inhibitors Novel agents: the next STAMPEDE? Docetaxel/Prednisolone plus… – Oblimersen – Bevacizumab – Clusterin antisense – Atrasentan – Vitamin D All being tested separately! Novel agents: the next STAMPEDE? Docetaxel/Prednisolone plus… – Oblimersen – Bevacizumab – Clusterin antisense – Atrasentan – Vitamin D EORTC CALGB NCIC SWOG Various All being tested separately! Prostate Cancer in Wales: punching above our weight!! Human tissue for research – Wales Cancer Bank Active Monitoring studies – ‘Non-drug’ interventions Neo-adjuvant studies – With tissue available after RP The Cardiff MDT