ProBio Trial Progress Portal

Last updated: November 29, 2025
Accessibility level: Public

This report contains summary information of the enrollment and follow-up of patients in ProBio.
All the data are anonymized and blinded on both the subjects’ biomarker profile and randomized therapy.

This is a computer-generated document. Contact the author Alessio Crippa for any question.

Overall information on study design, enrollment, and follow-up is reported in the Home. Separate information for metastatic Hormone-Sensitive Prostate Cancer with detectable (mHSPC) and undetectable ctDNA (mHSPC undetectable), and for metastatic Castration-Resistant Prostate Cancer (mCRPC) patients are reported in dedicated tabs.

The results are presented in separated tabs:

  • Study information:
    • Report summary;
    • Protocol synopsis;
    • Protocol amendment history;
    • Stopping rules.
  • Enrollment information:
    • indicators of enrolled and randomized patients, and enrolling centers;
    • maps of recruiting centers;
    • enrolled patients over time (by center);
    • info centers.
  • Follow-up variable:
    • flowchart;
    • classification patients (randomized, incomplete, excluded);
  • Data Manager:
    • info on incomplete patients;
    • info on excluded patients;
    • info on randomized patients.

Report summary

PROTOCOL TITLE: An outcome-adaptive and randomised multi-arm biomarker driven study in patients with metastatic prostate cancer
EUDRACT NUMBER: 2018-002350-78
CLINICALTRIALS.GOV NUMBER: NCT03903835
PROTOCOL VERSION: v6.0
PRINCIPAL INVESTIGATOR: Henrik Grönberg,
Professor, Department of Medical Epidemiology and Biostatistics,
Karolinska Institutet, Sweden
DATE REPORT ISSUED: 2025 November, 29
DATA CUTOFF DATE: 2025 November, 28
PREPARED BY: Alessio Crippa, PhD


Protocol synopsis

Protocol Title: ProBio is an outcome-adaptive and randomised multi-arm biomarker driven study in patients with metastatic prostate cancer
Principal Investigator: Henrik Grönberg, Professor
Study activation date: January 29th, 2019
Planned Accrual Period: Patients will be followed from time of consent through the study duration
Study design: ProBio is an outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic prostate cancer
Study objectives: To determine whether therapy class choice based on a biomarker signature can improve Progression Free Survival (PFS) compared to standard of care in patients with metastatic prostate cancer
Treatment Description: Patients can be randomized to either the control group (i.e. standard-of-care) or to the experimental arm consisting of one of the following therapy classes: AR signalling inhibitors (ARSi), Taxane-based chemotherapy, Platinum-based chemotherapy, and PARP Inhibitor (PARPi)
Inclusion criteria: Male patients, aged above 18 years, with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing
- Newly diagnosed (i.e. de novo) metastatic hormone-sensitive prostate cancer (mHSPC) or
- First-line mCRPC, i.e. first evidence of progressive metastatic prostate cancer under castrate levels (<50 ng/dL) of serum testosterone, as defined by the EAU guidelines, encompassing biochemical and/or radiologic progression criteria
Exclusion criteria: Upon entering the mHSPC phase of the trial, prior systemic therapy (including ADT) is not allowed. Patients with mCRPC may not enter the trial when they have already received prior systemic therapy (with the exception of standard ADT) for mCRPC. Patients with mCRPC can enter the mCRPC phase of the trial regardless which prior therapy they received in the hormone-sensitive or non-metastatic CRPC phase
Study outcomes (mHSPC): PFS is defined as the time to development of castration-resistance, as defined by EAU guidelines (Cornford et al. 2017), i.e. whilst having castration levels of serum testosterone (<50ng/dL or 1.7 nmol/L) the time from randomisation to biochemical and/or radiologic progression
Study outcomes (mCRPC): PFS is defined as the time to no longer clinical benefit (NLCB), as defined by Prostate Cancer Working Group (PCWG) 3, i.e. the date and the specific reason(s) a therapy was ultimately discontinued, by evaluating biochemical, radiologic, and clinical progression criteria



Stopping rules

Graduation: \(n \ge 25\) for the evaluated treatment-signature combination
\(\pi_s \ge 85\%\), \(\pi_s\) being the probability of superiority for the evaluated treatment vs the control within the biomarker signature
\(\pi_j \ge 70\%\), \(\pi_j\) being the probability of superiority for the evaluated treatment vs the control within all the biomarker subgroup combinations belonging to the evaluated signature
Futility: \(n \ge 25\) for the evaluated treatment-signature combination
\(\pi_s \le 30\%\), \(\pi_s\) being the probability of superiority for the evaluated treatment vs the control within the biomarker signature
\(\pi_j \le 50\%\), \(\pi_j\) being the probability of superiority for the evaluated treatment vs the control within all the biomarker subgroup combinations belonging to the evaluated signature
Max patients: \(n \ge 150\)

More information on the aims, study design and statistical aspects are available at http://rpubs.com/alecri/useR2019.

NB At least 5 patients are required in each biomarker subgroup combination.
Have a look at slide 20 for an intuition of the definition of a probability of superiority.

Visual indicators for progressive number of enrolling centers, enrolled patients (who signed the informed consent form), randomized patients.

Center maps


Interactive map with summary numbers of enrollment, randomization status, and progression for the recruiting centers.


Accrual plot


Cumulative number of enrolled patients over time (consent date). Solid line includes men enrolled in the study (also not randomized), dashed line includes only randomized patients.


Info centers

Summary numbers of enrollment for the recruiting centers.
Center City
ntot
nrandomized
nexcluded
nincomplete
daylastenrolled
Enrolled Randomized Excluded Incomplete Days from last enrollment
Sweden
Capio Saint Göran's Hospital Stockholm 113 76 35 2 1
Karolinska Universitetssjukhuset Stockholm 60 38 16 6 2
Länssjukhuset i Sundsvall Sundsvall 55 40 15 0 59
Akademiska Sjukhuset Uppsala 48 29 19 0 3
Länssjukhuset i Ryhov Jönköping 45 30 15 0 109
Norrlands Universitetssjukhus Umeå 38 24 13 1 10
Växjö lasarett Sweden 26 14 10 2 9
Länssjukhuset i Kalmar Kalmar 24 13 9 2 18
Länssjukhuset i Karlstad Karlstad 23 13 10 0 528
Falu lasarett Falun 12 7 5 0 45
Södra Älvsborgs sjukhus Borås 8 6 2 0 323
Universitetssjukhuset Örebro Örebro 4 2 2 0 262
Norway
Stavanger Universitetssjukehus Stavanger 90 54 35 1 2
Akershus University Hospital Akershus University Hospital 55 28 27 0 3
Sörlandet Sykehus Kristiansand Kristiansand 31 21 8 2 9
Universitetssykehuset Nord-Norge Tromsö Tromsø 22 15 6 1 2
Sykehuset Östfold Kalnes Norway 20 14 6 0 18
Ålesund Sjukehus Ålesund 18 7 11 0 106
Belgium
GZA Sint-Augustinus Antwerp 77 51 26 0 24
UZ Gent Ghent 57 33 23 1 1
AZ St-Jan Brugge Bruges 53 32 20 1 2
AZ Groeninge Kortrijk 43 30 13 0 22
CHU Liège Liège 41 30 11 0 54
OLV Aalst Aalst 34 15 19 0 9
AZ Nikolaas Sint-Niklaas 32 20 11 1 23
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 25 19 6 0 40
Helora Hospital La Louviere Site Jolimont La Louvière 17 7 9 1 36
AZ Damiaan Ostend 15 8 7 0 290
AZ St-Lucas Brugge AZ Sint-Lucas 9 2 7 0 709
AZ Maria-Middelares Belgium 3 3 0 0 46
Jessa Ziekenhuis Hasselt 2 2 0 0 1026
Switzerland
University Hospital Basel Basel 43 30 13 0 65
St. Claraspital Basel 9 6 3 0 75
Kantonspital Aarau Aarau 2 2 0 0 3

Flowchart


Patient Enrollment Flowchart. Patients may enter ProBio either as metastatic hormone-sensitive (mHS) or as first-line metastatic castration-resistant (mCR). Patients with progressive disease may be re-randomized for up to two subsequent treatment lines for mCR prostate cancer. mHS patients with undetectable ctDNA will be enrolled in the de-escalation trial, whereas mCR patients with undetectable ctDNA will be excluded. Additional reasons for exclusion include technical failure of the liquid biopsy test, detection of MSI+, or other exclusion criteria.

Pie chart

Pie chart showing randomization status of enrolled patients. Incomplete refers to patients who have not yet been randomized due to pending ctDNA analysis. Low ctDNA includes patients with undetectable ctDNA at first randomization in the mCR setting, or those with undetectable ctDNA enrolled prior to protocol version 6.0.

This panel is available only for data manager.



The results are presented in separated tabs:

  • Enrollment information:
    • indicators of enrolled and randomized patients, and enrolling centers;
    • maps of recruiting centers;
    • enrolled patients over time (by center);
    • inclusion rate;
    • info centers.
  • Follow-up variable:
    • classification patients (randomized, incomplete, excluded);
    • flowchart;
    • swimmer plot.
  • Baseline variables (tables 1 for):
    • clinical characteristics;
    • metastatic burden profile;
    • routine blood diagnostics.
  • Biomarkers:
    • prevalence of signatures and subgroup combinations (by treatment).
  • Therapies:
    • prevalence of therapies in the control group;
    • overlap of biomarker signatures by therapies.
  • Number of Progressions:
    • flowchart;
    • type of progressions (upset and alluvial plot);
    • response evaluation.
  • Evaluation of therapies:
    • results by therapy classes;
    • posterior STR/HR distributions;
    • PFS curves (Kaplan Meier and posterior).
  • Serious adverse events.

Visual indicators for progressive number of enrolling centers, enrolled patients (who signed the informed consent form), randomized and re-randomized (2nd randomization) patients.

Center maps


Interactive map with summary numbers of enrollment, randomization status, and progression for the recruiting centers.


Accrual plot


Cumulative number of enrolled patients over time (consent date). Solid line includes men enrolled in the study (also not randomized), dashed line includes only randomized patients.


Inclusion rate


Randomization rate by quarters of year (randomized/signed ICF) over time overall (dashed lines) and by country (solid coloured lines).


Info centers

Summary numbers of enrollment for the recruiting centers.
Center City Enrolled Randomized Excluded Incomplete days from last enrollment
Belgium
AZ St-Jan Brugge Bruges 22 13 9 0 52
UZ Gent Ghent 11 6 5 0 16
AZ Groeninge Kortrijk 28 21 7 0 23
OLV Aalst Aalst 6 2 4 0 243
AZ Damiaan Ostend 10 6 4 0 323
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 16 12 4 0 50
AZ St-Lucas Brugge Bruges 3 0 3 0 716
CHU Liège Liège 28 21 7 0 65
AZ Nikolaas Belgium 19 13 5 1 23
GZA Sint-Augustinus Antwerp 43 29 14 0 24
Helora Hospital La Louviere Site Jolimont La Louvière 10 3 7 0 87
AZ Maria-Middelares Belgium 2 2 0 0 86
Norway
Akershus University Hospital Oslo 24 14 10 0 23
Stavanger Universitetssjukehus Norway 39 28 10 1 3
Universitetssykehuset Nord-Norge Tromsö Tromsø 7 4 2 1 3
Ålesund Sjukehus Ålesund 5 2 3 0 221
Sörlandet Sykehus Kristiansand Kristiansand 24 15 7 2 9
Sykehuset Östfold Kalnes Norway 15 9 6 0 18
Sweden
Capio Saint Göran's Hospital Stockholm 50 37 11 2 1
Karolinska Universitetssjukhuset Sweden 14 10 2 2 10
Akademiska Sjukhuset Uppsala 13 7 6 0 113
Norrlands Universitetssjukhus Sweden 13 6 6 1 17
Länssjukhuset i Sundsvall Sundsvall 24 20 4 0 200
Länssjukhuset i Ryhov Jönköping 5 4 1 0 109
Växjö lasarett Sweden 6 2 2 2 10
Länssjukhuset i Kalmar Kalmar 13 8 5 0 18
Falu lasarett Falun 1 1 0 0 45
Switzerland
University Hospital Basel Basel 34 23 11 0 109
St. Claraspital Basel 4 4 0 0 457

Flowchart


Patient enrolled flowchart. Patients signing consent may not be randomized because of low circulated tumour DNA or techincal failure in liquid biospy test, MSI+ dection, or becaue of exclusion criteria. After first progression, patients in the experimental arms can be re-randomized to a second experimental treatment, while progressive patients in the control arm remain as control.

Pie chart

Pie chart for randomization status of enrolled patients. Incomplete patients has not yet been randomized because of pending ctDNA analysis.

Swimmer plot



This panel is available only for ProBio investigators or members in the DMSB.

Clinical characteristics by study arm of randomized participants

Metastatic burden profile by study arm of randomized participants

Routine blood diagnostics by study arm of randomized participants

This panel is available only for ProBio investigators or members in the DMSB.

Prevalence of biomarker signatures

Prevalence of biomarker subgroup combinations

Pie chart subgroup combinations

 

Prevalence of biomarker signatures across therapy classes

This panel is available only for ProBio investigators or members in the DMSB.

Prevalence of therapies in the control group

Overlap of biomarker signatures by therapies.

This panel is available only for ProBio investigators or members in the DMSB.

This panel is available only for members in the DMSB.

This panel is available only for ProBio investigators or members in the DMSB.

Visual indicators for progressive number of enrolling centers, enrolled patients (who signed the informed consent form), randomized.

Center maps


Interactive map with summary numbers of enrollment, randomization status, and progression for the recruiting centers.


Info centers

Summary numbers of enrollment for the recruiting centers.
Center City Enrolled Randomized Excluded days from last enrollment
Belgium
AZ St-Jan Brugge Bruges 5 5 0 85
UZ Gent Ghent 4 4 0 30
AZ Groeninge Belgium 4 4 0 100
OLV Aalst Aalst 3 3 0 100
Ziekenhuis Oost-Limburg Belgium 1 1 0 157
CHU Liège Liège 1 1 0 170
AZ Nikolaas Belgium 1 1 0 40
GZA Sint-Augustinus Antwerp 5 5 0 25
Helora Hospital La Louviere Site Jolimont Jolimont 2 2 0 103
AZ Maria-Middelares Belgium 1 1 0 46
Norway
Akershus University Hospital Oslo 2 2 0 46
Stavanger Universitetssjukehus Stavanger 1 1 0 53
Universitetssykehuset Nord-Norge Tromsö Tromsø 4 4 0 26
Ålesund Sjukehus Ålesund 1 1 0 107
Sörlandet Sykehus Kristiansand Kristiansand 1 1 0 99
Sykehuset Östfold Kalnes Østfold 3 3 0 37
Sweden
Capio Saint Göran's Hospital Stockholm 2 2 0 52
Karolinska Universitetssjukhuset Stockholm 3 3 0 64
Norrlands Universitetssjukhus Umeå 1 1 0 151
Länssjukhuset i Sundsvall Sundsvall 3 3 0 59
Växjö lasarett Växjö 1 1 0 101
Switzerland
University Hospital Basel Basel 4 4 0 65
St. Claraspital Basel 1 1 0 82
Kantonspital Aarau Aarau 1 1 0 26

The results are presented in separated tabs:

  • Enrollment information:
    • indicators of enrolled and randomized patients, and enrolling centers;
    • maps of recruiting centers;
    • enrolled patients over time (by center);
    • inclusion rate;
    • info centers.
  • Follow-up variable:
    • therapies timeline;
    • classification patients (randomized, incomplete, excluded);
    • flowchart;
    • swimmer plot.
  • Baseline variables (tables 1 for):
    • clinical characteristics;
    • metastatic burden profile;
    • routine blood diagnostics;
    • baseline variables by randomization status.
  • Biomarkers (first randomization):
    • prevalence of signatures and subgroup combinations (by treatment);
    • changes after progression.
  • Therapies:
    • prevalence of therapies in the control group;
    • overlap of biomarker signatures by therapies.
  • Number of Progressions:
    • flowchart;
    • type of progressions (upset and alluvial plot);
    • response evaluation.
  • Evaluation of therapies:
    • results by therapy classes;
    • posterior STR/HR distributions;
    • PFS curves (Kaplan Meier and posterior).
  • Serious adverse events.

Visual indicators for progressive number of enrolling centers, enrolled patients (who signed the informed consent form), randomized and re-randomized (2nd randomization) patients.

Center maps


Interactive map with summary numbers of enrollment, randomization status, and progression for the recruiting centers.


Accrual plot


Cumulative number of enrolled patients over time (consent date). Solid line includes men enrolled in the study (also not randomized), dashed line includes only randomized patients.


Inclusion rate


Randomization rate by quarters of year (randomized/signed ICF) over time overall (dashed lines) and by country (solid coloured lines).


Info centers

Summary numbers of enrollment for the recruiting centers.
Center City Enrolled Randomized Re-randomized Excluded Incomplete days from last enrollment
Belgium
AZ St-Jan Brugge Bruges 22 11 5 11 0 240
UZ Gent Ghent 40 22 10 18 0 338
AZ Groeninge Kortrijk 13 7 4 6 0 362
OLV Aalst Aalst 24 9 1 15 0 233
AZ Damiaan Ostend 6 3 0 3 0 290
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 9 7 5 2 0 792
AZ St-Lucas Brugge AZ Sint-Lucas 6 2 0 4 0 971
CHU Liège Liège 18 14 7 4 0 325
Jessa Ziekenhuis Hasselt 2 2 1 0 0 1045
AZ Nikolaas Sint-Niklaas 13 7 2 6 0 374
GZA Sint-Augustinus Antwerp 30 18 4 12 0 333
Helora Hospital La Louviere Site Jolimont La Louvière 3 1 0 2 0 347
Norway
Akershus University Hospital Akershus University Hospital 28 11 6 17 0 219
Stavanger Universitetssjukehus Stavanger 50 25 9 25 0 208
Universitetssykehuset Nord-Norge Tromsö Tromsø 11 7 0 4 0 471
Ålesund Sjukehus Ålesund 12 4 2 8 0 302
Sörlandet Sykehus Kristiansand Kristiansand 7 6 1 1 0 254
Sykehuset Östfold Kalnes Norway 3 2 0 1 0 165
Sweden
Capio Saint Göran's Hospital Stockholm 63 38 15 25 0 247
Karolinska Universitetssjukhuset Stockholm 39 25 13 14 0 435
Akademiska Sjukhuset Uppsala 35 22 10 13 0 324
Norrlands Universitetssjukhus Umeå 24 17 7 7 0 296
Länssjukhuset i Sundsvall Sundsvall 31 21 7 10 0 283
Länssjukhuset i Ryhov Jönköping 40 26 15 14 0 431
Växjö lasarett Sweden 19 11 5 8 0 324
Länssjukhuset i Karlstad Karlstad 23 13 8 10 0 529
Länssjukhuset i Kalmar Kalmar 9 5 3 4 0 655
Falu lasarett Falun 11 6 1 5 0 403
Södra Älvsborgs sjukhus Borås 8 6 1 2 0 324
Universitetssjukhuset Örebro Örebro 4 2 1 2 0 269
Switzerland
University Hospital Basel Basel 12 9 1 3 0 464
St. Claraspital Basel 4 1 0 3 0 452

Flowchart


Patient enrolled flowchart. Patients signing consent may not be randomized because of low circulated tumour DNA or techincal failure in liquid biospy test, MSI+ dection, or becaue of exclusion criteria. After first progression, patients in the experimental arms can be re-randomized to a second experimental treatment, while progressive patients in the control arm remain as control.

Pie chart

Pie chart for randomization status of enrolled patients. Incomplete patients has not yet been randomized because of pending ctDNA analysis.

Swimmer plot


This panel is available only for ProBio investigators or members in the DMSB.

Clinical characteristics by study arm of randomized participants

Metastatic burden profile by study arm of randomized participants

Routine blood diagnostics by study arm of randomized participants

Treatment history by study arm of randomized participants

     

Baseline variables by randomization status

This panel is available only for ProBio investigators or members in the DMSB.

Prevalence of biomarker signatures

Prevalence of biomarker subgroup combinations

Pie chart subgroup combinations

Prevalence of biomarker signatures across therapy classes. Only first randomizations are included.

Change in subgroup combination

This panel is available only for ProBio investigators or members in the DMSB.

Prevalence of therapies in the control group

Overlap of biomarker signatures by therapies.

This panel is available only for ProBio investigators or members in the DMSB.

Flowchart

Type of progressions

Alluvial plot

 

Swimmer plot for response evaluation

This panel is available only for members in the DMSB.

This panel is available only for ProBio investigators or members in the DMSB.