ProBio Trial Progress Portal

Last updated: February 03, 2026
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: 2026 February, 03
DATA CUTOFF DATE: 2026 February, 02
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 78 35 0 67
Karolinska Universitetssjukhuset Stockholm 62 45 16 1 5
Länssjukhuset i Sundsvall Sundsvall 59 43 16 0 26
Akademiska Sjukhuset Uppsala 48 29 19 0 82
Länssjukhuset i Ryhov Jönköping 47 31 15 1 5
Norrlands Universitetssjukhus Umeå 41 28 13 0 46
Växjö lasarett Sweden 26 16 9 1 15
Länssjukhuset i Kalmar Kalmar 25 13 10 2 31
Länssjukhuset i Karlstad Karlstad 23 13 10 0 594
Falu lasarett Falun 12 7 5 0 111
Södra Älvsborgs sjukhus Borås 8 6 2 0 389
Universitetssjukhuset Örebro Örebro 4 2 2 0 328
Norway
Stavanger Universitetssjukehus Stavanger 91 55 35 1 28
Akershus University Hospital Akershus University Hospital 58 29 27 2 7
Sörlandet Sykehus Kristiansand Kristiansand 34 22 9 3 5
Universitetssykehuset Nord-Norge Tromsö Tromsø 27 20 6 1 12
Sykehuset Östfold Kalnes Norway 21 15 6 0 12
Ålesund Sjukehus Ålesund 19 8 11 0 29
Belgium
GZA Sint-Augustinus Antwerp 81 54 26 1 6
UZ Gent Ghent 58 35 23 0 12
AZ St-Jan Brugge Bruges 57 36 20 1 5
AZ Groeninge Kortrijk 47 32 13 2 7
CHU Liège Liège 45 33 11 1 4
OLV Aalst Aalst 36 17 19 0 6
AZ Nikolaas Sint-Niklaas 32 21 11 0 89
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 29 23 6 0 6
Helora Hospital La Louviere Site Jolimont La Louvière 18 7 9 2 46
AZ Damiaan Ostend 15 8 7 0 356
AZ St-Lucas Brugge AZ Sint-Lucas 9 2 7 0 775
AZ Maria-Middelares Belgium 6 5 0 1 12
Jessa Ziekenhuis Hasselt 2 2 0 0 1092
Switzerland
University Hospital Basel Basel 46 32 14 0 6
St. Claraspital Basel 9 6 3 0 141
Kantonspital Aarau Aarau 4 4 0 0 48

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 23 13 9 1 8
UZ Gent Ghent 11 6 5 0 82
AZ Groeninge Kortrijk 30 21 7 2 7
OLV Aalst Aalst 6 2 4 0 309
AZ Damiaan Ostend 10 6 4 0 389
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 18 14 4 0 21
AZ St-Lucas Brugge Bruges 3 0 3 0 782
CHU Liège Liège 30 22 7 1 8
AZ Nikolaas Belgium 18 13 5 0 152
GZA Sint-Augustinus Antwerp 44 29 14 1 12
Helora Hospital La Louviere Site Jolimont La Louvière 11 3 7 1 46
AZ Maria-Middelares Belgium 5 4 0 1 13
Norway
Akershus University Hospital Oslo 27 15 10 2 7
Stavanger Universitetssjukehus Norway 40 29 10 1 29
Universitetssykehuset Nord-Norge Tromsö Tromsø 9 6 2 1 13
Ålesund Sjukehus Ålesund 6 3 3 0 32
Sörlandet Sykehus Kristiansand Kristiansand 27 16 8 3 5
Sykehuset Östfold Kalnes Norway 15 9 6 0 84
Sweden
Capio Saint Göran's Hospital Stockholm 50 39 11 0 67
Karolinska Universitetssjukhuset Sweden 16 14 2 0 20
Akademiska Sjukhuset Uppsala 13 7 6 0 179
Norrlands Universitetssjukhus Sweden 15 9 6 0 57
Länssjukhuset i Sundsvall Sundsvall 27 22 5 0 26
Länssjukhuset i Ryhov Jönköping 7 5 1 1 5
Växjö lasarett Sweden 6 3 2 1 15
Länssjukhuset i Kalmar Kalmar 14 8 6 0 36
Falu lasarett Falun 1 1 0 0 111
Switzerland
University Hospital Basel Basel 36 24 12 0 29
St. Claraspital Basel 4 4 0 0 523

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 10 10 0 68
UZ Gent Ghent 6 6 0 71
AZ Groeninge Belgium 6 6 0 43
OLV Aalst Aalst 4 4 0 92
Ziekenhuis Oost-Limburg Belgium 2 2 0 69
CHU Liège Liège 2 2 0 54
AZ Nikolaas Belgium 2 2 0 89
GZA Sint-Augustinus Antwerp 7 7 0 35
Helora Hospital La Louviere Site Jolimont Jolimont 3 3 0 124
AZ Maria-Middelares Belgium 1 1 0 112
Norway
Akershus University Hospital Oslo 3 3 0 81
Stavanger Universitetssjukehus Stavanger 1 1 0 119
Universitetssykehuset Nord-Norge Tromsö Tromsø 6 6 0 48
Ålesund Sjukehus Ålesund 1 1 0 173
Sörlandet Sykehus Kristiansand Kristiansand 1 1 0 165
Sykehuset Östfold Kalnes Østfold 3 3 0 103
Sweden
Capio Saint Göran's Hospital Stockholm 2 2 0 118
Karolinska Universitetssjukhuset Stockholm 6 6 0 69
Akademiska Sjukhuset Uppsala 1 1 0 85
Norrlands Universitetssjukhus Umeå 2 2 0 46
Länssjukhuset i Sundsvall Sundsvall 4 4 0 57
Växjö lasarett Växjö 2 2 0 76
Switzerland
University Hospital Basel Basel 4 4 0 131
St. Claraspital Basel 1 1 0 148
Kantonspital Aarau Aarau 4 4 0 48

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 0 306
UZ Gent Ghent 40 22 10 18 0 404
AZ Groeninge Kortrijk 13 7 4 6 0 428
OLV Aalst Aalst 24 9 1 15 0 299
AZ Damiaan Ostend 6 3 0 3 0 356
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 9 7 5 2 0 858
AZ St-Lucas Brugge AZ Sint-Lucas 6 2 0 4 0 1037
CHU Liège Liège 18 14 7 4 0 391
Jessa Ziekenhuis Hasselt 2 2 1 0 0 1111
AZ Nikolaas Sint-Niklaas 13 7 2 6 0 440
GZA Sint-Augustinus Antwerp 30 18 4 12 0 399
Helora Hospital La Louviere Site Jolimont La Louvière 3 1 0 2 0 413
Norway
Akershus University Hospital Akershus University Hospital 28 11 6 17 0 285
Stavanger Universitetssjukehus Stavanger 50 25 9 25 0 274
Universitetssykehuset Nord-Norge Tromsö Tromsø 11 7 0 4 0 537
Ålesund Sjukehus Ålesund 12 4 2 8 0 368
Sörlandet Sykehus Kristiansand Kristiansand 7 6 1 1 0 320
Sykehuset Östfold Kalnes Norway 3 2 0 1 0 231
Sweden
Capio Saint Göran's Hospital Stockholm 63 38 15 25 0 313
Karolinska Universitetssjukhuset Stockholm 39 25 13 14 0 501
Akademiska Sjukhuset Uppsala 35 22 10 13 0 390
Norrlands Universitetssjukhus Umeå 24 17 7 7 0 362
Länssjukhuset i Sundsvall Sundsvall 31 21 7 10 0 349
Länssjukhuset i Ryhov Jönköping 40 26 15 14 0 497
Växjö lasarett Sweden 19 11 5 8 0 390
Länssjukhuset i Karlstad Karlstad 23 13 8 10 0 595
Länssjukhuset i Kalmar Kalmar 9 5 3 4 0 721
Falu lasarett Falun 11 6 1 5 0 469
Södra Älvsborgs sjukhus Borås 8 6 1 2 0 390
Universitetssjukhuset Örebro Örebro 4 2 1 2 0 335
Switzerland
University Hospital Basel Basel 12 9 1 3 0 530
St. Claraspital Basel 4 1 0 3 0 518

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.