SUNRISE Enrolment & Eventing Simulation 1st/2nd Look-in
May 4th, 2015 SUNRISE day #490, 1 year, 4 months and 5 days into the clinical trial.
ATTENTION: This post hold simulation data parameters which are NOT EXACT PREDICTIONS and depending on the precision of some assumptions the real results may differ.
FACTUAL DATA SOURCE
Start Date : 31 Dec 2013 (PPHM PR 30 DEC 2013)
Start enrolment : JAN 2014 (PPHM PR 30 DEC 2013)
Planned End of enrolment : DEC 2015 (clinicaltrails.gov)
Planned End of trial : DEC 2016 (clinicaltrails.gov)
Announced # treatment centres : more then 100. (Shan on a PPHM quarterly/CC)
Current # of treatment centres open : 158 (clinicaltrails.gov)
Most were open on : Q3/2014 (clinicaltrails.gov history files)
Simulation Dates Used : Real Opening Dates per centre (clinicaltrails.gov history files)
Start recruitment : recruiting as of opening day (clinicaltrails.gov history files)
Last ON TRACK report by PPHM : March 2015 (Quarterly/CC March 12, 2015)
Total # patients in trail : 582 (clinicaltrials.gov)
Arm A : Docetaxel+Placebo Control arm
Arm B : Docetaxel+Bavituximab 3mg/Kg arm
Randomizing Placebo Ctrl/Bavi : 1/1 (clinicaltrails.gov)
# of planned look-ins : 2 (Quarterly/Annual CC's)
1st Look In # Events : 192 (since SK's presentation @ ROTH 33%)
2nd Look In # Events : 291 (since SK's presentation @ ROTH 50%)
ESTIMATES/ASUPTIONS FOR ENROLMENT SIMULATION
# patients available at centre open : 0
Days needed to enrol 1 patient/centre : 112 (about 3.5 month) (IHub posters educated consensus)
Max Patients per Centre : 4 (Average)
Placebo Eventing days : 210 (7 months) (Golfho's assumption)
Bavi Eventing days : 365 (12 months) (Golfho's assumption)
PPHM PII Placebo Eventing days : 145 (5.6 months) (Chicago Spet 7th 2012 conference)
PPHM PII Bavi Eventing days : 365 (12 months) (idem, between 1mg 11.5 and 3mg 13.5)
Historical Placebo Eventing days : 110 (3.5 months) (for comparable ECOG groups)
ESTIMATES FOR EVENTING
Patients days mid-of-period : 56 (assumed enrolled mid of 112 days)
No eventing in first period : 112 (patients in 1st 112 days excluded from eventing)
SIMULATION RESULTS per 4th APR 2015
Patients Enrolled : 410
Evented Placebo Patients : 134
Evented Bavi Patients : 73
Total Evented : 207
Remaining Events Needed for 1st Look-in: 0 (READY)
Remaining Events Needed for 2nd Look-in: 85
Placebo Patients Alive : 71
Bavi Patients Alive : 132
Patients Alive : 203
So if this simulation is correct, the next time the DMC meets they should be able to perform a first look-in.
The results must then appear for the committee, be discussed and an advise to PPHM must be made.
In short this can be:
- DISCONTINUE FUTILITY : When the results show there is very little chance the trial will ever deliver the expected end-points.
- CONTINUE : All is within normal parameters.
- DISCONTINUE STOP : Early STOP advice when results are already showing that they can be approved by the FDA.
- DISCONTINUE ETHICS : STOP, put control arm patients on Bavituximab.
In the TWO last cases all patients will receive Bavituximab. PPHM may go against an advise.
It is not because the DMC advise a CONTINUE that PPHM MUST continue. The same goes for FUTILITY, etc.
Whether we get PR's will depend in how much such FDA DMC letter is a material event and if not if PPHM wants or does not want to disclose interim data (they had bad experiences with that in PII). If they don't PR the look-in results we may wake-up one morning on a final FDA PIII approval but that would then be for Q4/2015 at the earliest I think. I do however not anticipate that possibility.
AI
