ProBio Trial Progress Portal

Last updated: September 01, 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 September, 01
DATA CUTOFF DATE: 2026 August, 31
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 119 84 35 0 21
Karolinska Universitetssjukhuset Stockholm 72 55 17 0 33
Länssjukhuset i Sundsvall Sundsvall 65 49 16 0 75
Länssjukhuset i Ryhov Jönköping 56 39 17 0 28
Akademiska Sjukhuset Uppsala 48 29 19 0 292
Norrlands Universitetssjukhus Umeå 46 31 13 2 6
Länssjukhuset i Kalmar Kalmar 28 16 10 2 7
Växjö lasarett Sweden 27 18 9 0 225
Länssjukhuset i Karlstad Karlstad 26 15 11 0 28
Falu lasarett Falun 12 7 5 0 321
Södra Älvsborgs sjukhus Borås 8 6 2 0 599
Universitetssjukhuset Örebro Örebro 4 2 2 0 538
Norway
Stavanger Universitetssjukehus Stavanger 104 67 36 1 14
Akershus University Hospital Akershus University Hospital 62 34 28 0 18
Sörlandet Sykehus Kristiansand Kristiansand 44 32 11 1 11
Universitetssykehuset Nord-Norge Tromsö Tromsø 36 30 6 0 61
Sykehuset Östfold Kalnes Norway 26 18 7 1 6
Ålesund Sjukehus Ålesund 23 12 11 0 22
Belgium
GZA Sint-Augustinus Antwerp 96 68 27 1 5
UZ Gent Ghent 70 47 23 0 85
AZ St-Jan Brugge Bruges 58 38 20 0 165
CHU Liège Liège 54 43 11 0 8
AZ Groeninge Kortrijk 50 37 13 0 32
OLV Aalst Aalst 40 20 19 1 134
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 32 25 7 0 67
AZ Nikolaas Sint-Niklaas 32 21 11 0 299
Helora Hospital La Louviere Site Jolimont La Louvière 18 7 11 0 256
AZ Damiaan Ostend 15 8 7 0 566
AZ Maria-Middelares Belgium 13 12 1 0 8
AZ St-Lucas Brugge AZ Sint-Lucas 9 2 7 0 985
Jessa Ziekenhuis Hasselt 2 2 0 0 1302
Switzerland
University Hospital Basel Basel 57 42 14 1 12
St. Claraspital Basel 10 7 3 0 50
Kantonspital Aarau Aarau 6 5 0 1 92

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 14 9 0 168
UZ Gent Ghent 17 12 5 0 89
AZ Groeninge Kortrijk 28 21 7 0 299
OLV Aalst Aalst 8 3 4 1 137
AZ Damiaan Ostend 10 6 4 0 599
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 19 14 5 0 67
AZ St-Lucas Brugge Bruges 3 0 3 0 992
CHU Liège Liège 33 26 7 0 22
AZ Nikolaas Belgium 18 13 5 0 362
GZA Sint-Augustinus Antwerp 51 35 15 1 12
Helora Hospital La Louviere Site Jolimont La Louvière 11 3 8 0 256
AZ Maria-Middelares Belgium 6 5 1 0 35
Norway
Akershus University Hospital Oslo 29 18 11 0 18
Stavanger Universitetssjukehus Norway 43 31 11 1 14
Universitetssykehuset Nord-Norge Tromsö Tromsø 16 14 2 0 83
Ålesund Sjukehus Ålesund 9 6 3 0 22
Sörlandet Sykehus Kristiansand Kristiansand 32 21 10 1 11
Sykehuset Östfold Kalnes Norway 18 10 7 1 7
Sweden
Capio Saint Göran's Hospital Stockholm 54 43 11 0 21
Karolinska Universitetssjukhuset Sweden 22 19 3 0 48
Akademiska Sjukhuset Uppsala 13 7 6 0 389
Norrlands Universitetssjukhus Sweden 19 11 6 2 6
Länssjukhuset i Sundsvall Sundsvall 30 25 5 0 76
Länssjukhuset i Ryhov Jönköping 10 8 2 0 84
Växjö lasarett Sweden 5 3 2 0 287
Länssjukhuset i Karlstad Sweden 3 2 1 0 28
Länssjukhuset i Kalmar Kalmar 17 9 6 2 7
Falu lasarett Falun 1 1 0 0 321
Switzerland
University Hospital Basel Basel 41 28 12 1 13
St. Claraspital Basel 4 4 0 0 733
Kantonspital Aarau Aarau 1 0 0 1 97

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 13 13 0 218
UZ Gent Ghent 13 13 0 103
AZ Groeninge Belgium 11 11 0 35
OLV Aalst Aalst 8 8 0 183
Ziekenhuis Oost-Limburg Belgium 5 5 0 145
CHU Liège Liège 7 7 0 81
AZ Nikolaas Belgium 2 2 0 299
GZA Sint-Augustinus Antwerp 14 14 0 81
Helora Hospital La Louviere Site Jolimont Jolimont 3 3 0 334
AZ Maria-Middelares Belgium 6 6 0 155
Norway
Akershus University Hospital Oslo 5 5 0 181
Stavanger Universitetssjukehus Stavanger 10 10 0 34
Universitetssykehuset Nord-Norge Tromsö Tromsø 9 9 0 61
Ålesund Sjukehus Ålesund 2 2 0 209
Sörlandet Sykehus Kristiansand Kristiansand 6 6 0 71
Sykehuset Östfold Kalnes Østfold 6 6 0 180
Sweden
Capio Saint Göran's Hospital Stockholm 4 4 0 89
Karolinska Universitetssjukhuset Stockholm 11 11 0 33
Akademiska Sjukhuset Uppsala 1 1 0 295
Norrlands Universitetssjukhus Umeå 3 3 0 132
Länssjukhuset i Sundsvall Sundsvall 7 7 0 75
Länssjukhuset i Ryhov Jönköping 6 6 0 29
Växjö lasarett Växjö 3 3 0 225
Länssjukhuset i Kalmar Kalmar 2 2 0 83
Switzerland
University Hospital Basel Basel 9 9 0 33
St. Claraspital Basel 2 2 0 53
Kantonspital Aarau Aarau 5 5 0 95

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 0 516
UZ Gent Ghent 40 22 10 18 0 614
AZ Groeninge Kortrijk 13 7 4 6 0 638
OLV Aalst Aalst 24 9 1 15 0 509
AZ Damiaan Ostend 6 3 0 3 0 566
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 9 7 5 2 0 1068
AZ St-Lucas Brugge AZ Sint-Lucas 6 2 0 4 0 1247
CHU Liège Liège 18 14 7 4 0 601
Jessa Ziekenhuis Hasselt 2 2 1 0 0 1321
AZ Nikolaas Sint-Niklaas 13 7 2 6 0 650
GZA Sint-Augustinus Antwerp 30 18 4 12 0 609
Helora Hospital La Louviere Site Jolimont La Louvière 3 1 0 2 0 623
Norway
Akershus University Hospital Akershus University Hospital 28 11 6 17 0 495
Stavanger Universitetssjukehus Stavanger 50 25 9 25 0 484
Universitetssykehuset Nord-Norge Tromsö Tromsø 11 7 0 4 0 747
Ålesund Sjukehus Ålesund 12 4 2 8 0 578
Sörlandet Sykehus Kristiansand Kristiansand 7 6 1 1 0 530
Sykehuset Östfold Kalnes Norway 3 2 0 1 0 441
Sweden
Capio Saint Göran's Hospital Stockholm 63 38 15 25 0 523
Karolinska Universitetssjukhuset Stockholm 39 25 13 14 0 711
Akademiska Sjukhuset Uppsala 35 22 10 13 0 600
Norrlands Universitetssjukhus Umeå 24 17 7 7 0 572
Länssjukhuset i Sundsvall Sundsvall 31 20 7 11 0 559
Länssjukhuset i Ryhov Jönköping 40 25 13 15 0 707
Växjö lasarett Sweden 19 12 5 7 0 600
Länssjukhuset i Karlstad Karlstad 23 13 8 10 0 805
Länssjukhuset i Kalmar Kalmar 9 5 3 4 0 931
Falu lasarett Falun 11 6 1 5 0 679
Södra Älvsborgs sjukhus Borås 8 6 1 2 0 600
Universitetssjukhuset Örebro Örebro 4 2 1 2 0 545
Switzerland
University Hospital Basel Basel 12 9 1 3 0 740
St. Claraspital Basel 4 1 0 3 0 728

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.