Studientätigkeit der SAKK beim Prostatakarzinom. Silke Gillessen, Onkologie, Kantonsspital St. Gallen

(1)

Studientätigkeit der SAKK beim Prostatakarzinom

Silke Gillessen, Onkologie,

Kantonsspital St. Gallen

(2)

Was bedeutet SAKK?

(3)

Wie ist die SAKK organisiert?

(4)

§  STAMPEDE: Phase III bei Patienten mit hormon-naiven Prostatakarzinom

§  SAKK 08/11: Phase III bei Patienten mit

kastrationsresistentem Prostatakarzinom nach Chemotherapie

§  SAKK 09/10: Phase III bei Patienten mit PSA-Anstieg nach radikaler Prostatektomie

Aktuell laufende Studien beim

Prostatakarzinom

(5)

STAMPEDE

Systemic Therapy in Advancing or Metasta9c Prostate cancer:

Evalua9on of Drug Eﬃcacy

Sponsor number: MRC PR08

ISRCTN number: ISRCTN78818544 EUDRACT number: 2004-000193-31 CTA number: 00316/0026/001-0001

(6)

MRC Clinical Trials Unit

Main Inclusion Criteria

Newly diagnosed high risk patients with:

•  At least two of: T3/4 or PSA≥40ng/ml or Gleason sum score 8-10

•  And intention to treat with radical radiotherapy

Newly diagnosed metastatic or nodal disease

•  Stage T

_any

N+ M0 or T

_any

N

_any

M+

Previously treated relapsing patients with either

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

•  PSA ≥ 20ng/ml

•  N+

•  M+

(7)

Hormone Therapy

Three acceptable approaches:

•  Bilateral orchidectomy

•  Total or sub-capsular

•  LHRH agonist or antagonist

•  Used according to local practice

•  Prophylactic anti-androgens recommended

Anti-androgen monotherapy is not allowed

(8)

Hormone Therapy Before Randomisation

It is preferable that patients are not started on hormones prior to randomisation but if they are then:

•  No more than 12 weeks of LHRH before randomisation

•  Orchidectomy should be performed no more than 12 weeks before randomisation

•  Patients with bilateral orchidectomy should start treatment within 4 weeks from surgery

•  No more than 14 weeks of anti-androgens before randomisation

•  PSA measurement MUST be taken before HT treatment starts!

(9)

Timelines: ini9al plans

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 ADT-alone

A

ADT + zoledronic acid B

ADT + docetaxel C

ADT + celecoxib D

ADT + zoledronic acid + docetaxel E

ADT + zoledronic acid + celecoxib F

Past accrual

Possible future accrual Follow-up

(10)

Accrual: end of Ac9vity Stage II

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 ADT-alone

A

Past accrual

(11)

Timelines: from Nov-‐2011

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

A

ADT + abiraterone G

ADT-alone

Past accrual

(12)

Timelines: from Jan-‐2013

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

A

ADT-alone

H ADT + RT

Past accrual

M1 only

(13)

Timelines: from March-‐2013

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

A

ADT-alone

H ADT + RT

Past accrual

M1 only

Geplant: Arm mit Abiraterone und Enzalutamid

(14)

STAMPEDE Accrual: April2013

Total recruitment (April 2013): 4097 patients

(15)

Current Recruitment Status

First patient

•  17

^th

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

•  3984

•  31st January 2013

•  Record month: Jan 2013 (114 patients recruited)

•  120 participating centres; 8 Swiss

centres

(16)

Patient Characteristics

Age (years) at randomisation median (quartiles) 65 (37-94) PSA (ng/ml) at randomisation median (quartiles) 65 (23-188) WHO performance status (0 Vs 1 Vs 2+) 3193 vs 858 vs

46 Bone mets at randomisation n (%) 2150 (52%)

RT planned n (%) 1189 (29%)

Type of HT: (LHRH vs bicalutamide vs orchidectomy) 4019 vs 54 vs 19

Data from April 2013

(17)

Patient characteristics

Newly diagnosed M1 61%

Newly diagnosed N+M0 21%

Newly diagnosed N0M0 14%

Previously treated 3%

Bone mets at randomisation 2,150 (52%) Liver mets at randomisation 61 (1.5%) Lung mets at randomisation 104 (3%) Distant node mets at randomisation 761 (19%) Other mets at randomisation 173 (4%)

(18)

STAMPEDE: Bisherige Resultate

•  Trial design erlaubt schnelle Rekrutierung und neue Behandlungen können effizienter und kostengünstiger evaluiert werden

•  Kein benefit für Celecoxib (FFS)

•  Bei 630 metastasierten Patienten: FFS: 12 Monate!

Mediane Zeit von FFS zu Tod: 22 Monate

Bessere 1. Linientherapie nötig!

Sydes M, Trials 2012; James ND, Lancet Oncol 2012; Clarke N, ASCO 2013

(19)

STAMPEDE

Patienten zuweisen:

daniel.engeler@kssg.ch aurelius.omlin@kssg.ch raeto.strebel@ksgr.ch

richard.cathomas@ksgr.ch

simona.berardi@sakk.ch

(20)

SAKK 08/11

Orteronel maintenance therapy in patients with metastatic castration resistant

prostate cancer and non-progressive

disease after first-line docetaxel therapy:

A multicenter randomized double-blind

placebo-controlled phase III trial

(21)

Orteronel

Adaptiert nach Attard G et al J Clin Oncol 2008

Nonsteroidaler CYP 17 Inhibitor, selektiv für 17, 20-lyase

Orteronel: Wirkmechanismus

(22)

Orteronel: Wirksamkeit

Adaptiert nach Agus DB et al ASCO 2011

(23)

Studien-Design

mCRPC Patienten

•  nicht-progredient unter docetaxel

•  Weitergeführte ADT

Stratifikation :

•  Zentrum

•  PS

•  Ort der Metastasen

Arm A 300mg Orteronel BID und BSC

Arm B

Placebo BID und BSC

Li fe lo ng fo llo w -u p

(24)

Studientätigkeit der SAKK beim Prostatakarzinom. Silke Gillessen, Onkologie, Kantonsspital St. Gallen