ProBio Trial Progress Portal

Last updated: December 21, 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 December, 21
DATA CUTOFF DATE: 2025 December, 20
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 77 35 1 23
Karolinska Universitetssjukhuset Stockholm 60 44 16 0 10
Länssjukhuset i Sundsvall Sundsvall 58 40 15 3 6
Akademiska Sjukhuset Uppsala 48 29 19 0 25
Länssjukhuset i Ryhov Jönköping 46 30 15 1 17
Norrlands Universitetssjukhus Umeå 41 25 13 3 2
Växjö lasarett Sweden 25 16 9 0 11
Länssjukhuset i Kalmar Kalmar 24 13 9 2 40
Länssjukhuset i Karlstad Karlstad 23 13 10 0 550
Falu lasarett Falun 12 7 5 0 67
Södra Älvsborgs sjukhus Borås 8 6 2 0 345
Universitetssjukhuset Örebro Örebro 4 2 2 0 284
Norway
Stavanger Universitetssjukehus Stavanger 90 54 35 1 24
Akershus University Hospital Akershus University Hospital 56 28 27 1 4
Sörlandet Sykehus Kristiansand Kristiansand 32 22 8 2 20
Universitetssykehuset Nord-Norge Tromsö Tromsø 24 16 6 2 4
Sykehuset Östfold Kalnes Norway 20 14 6 0 40
Ålesund Sjukehus Ålesund 18 7 11 0 128
Belgium
GZA Sint-Augustinus Antwerp 78 51 26 1 19
UZ Gent Ghent 57 34 23 0 23
AZ St-Jan Brugge Bruges 54 33 20 1 10
AZ Groeninge Kortrijk 44 30 13 1 3
CHU Liège Liège 43 30 11 2 6
OLV Aalst Aalst 34 15 19 0 46
AZ Nikolaas Sint-Niklaas 32 21 11 0 45
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 27 20 6 1 2
Helora Hospital La Louviere Site Jolimont La Louvière 18 7 9 2 2
AZ Damiaan Ostend 15 8 7 0 312
AZ St-Lucas Brugge AZ Sint-Lucas 9 2 7 0 731
AZ Maria-Middelares Belgium 4 3 0 1 17
Jessa Ziekenhuis Hasselt 2 2 0 0 1048
Switzerland
University Hospital Basel Basel 44 30 14 0 13
St. Claraspital Basel 9 6 3 0 97
Kantonspital Aarau Aarau 4 2 0 2 4

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 24
UZ Gent Ghent 11 6 5 0 38
AZ Groeninge Kortrijk 29 21 7 1 3
OLV Aalst Aalst 6 2 4 0 265
AZ Damiaan Ostend 10 6 4 0 345
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 16 12 4 0 72
AZ St-Lucas Brugge Bruges 3 0 3 0 738
CHU Liège Liège 30 21 7 2 10
AZ Nikolaas Belgium 18 13 5 0 108
GZA Sint-Augustinus Antwerp 44 29 14 1 19
Helora Hospital La Louviere Site Jolimont La Louvière 10 3 7 0 109
AZ Maria-Middelares Belgium 3 2 0 1 18
Norway
Akershus University Hospital Oslo 25 14 10 1 4
Stavanger Universitetssjukehus Norway 39 28 10 1 25
Universitetssykehuset Nord-Norge Tromsö Tromsø 8 4 2 2 4
Ålesund Sjukehus Ålesund 5 2 3 0 243
Sörlandet Sykehus Kristiansand Kristiansand 25 16 7 2 20
Sykehuset Östfold Kalnes Norway 15 9 6 0 40
Sweden
Capio Saint Göran's Hospital Stockholm 50 38 11 1 23
Karolinska Universitetssjukhuset Sweden 15 13 2 0 31
Akademiska Sjukhuset Uppsala 13 7 6 0 135
Norrlands Universitetssjukhus Sweden 16 7 6 3 2
Länssjukhuset i Sundsvall Sundsvall 27 20 4 3 6
Länssjukhuset i Ryhov Jönköping 6 4 1 1 18
Växjö lasarett Sweden 5 3 2 0 33
Länssjukhuset i Kalmar Kalmar 13 8 5 0 40
Falu lasarett Falun 1 1 0 0 67
Switzerland
University Hospital Basel Basel 35 23 12 0 16
St. Claraspital Basel 4 4 0 0 479
Kantonspital Aarau Aarau 2 0 0 2 4

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 6 6 0 45
UZ Gent Ghent 6 6 0 27
AZ Groeninge Belgium 4 4 0 122
OLV Aalst Aalst 4 4 0 48
Ziekenhuis Oost-Limburg Belgium 2 2 0 25
CHU Liège Liège 1 1 0 192
AZ Nikolaas Belgium 2 2 0 45
GZA Sint-Augustinus Antwerp 5 5 0 47
Helora Hospital La Louviere Site Jolimont Jolimont 3 3 0 80
AZ Maria-Middelares Belgium 1 1 0 68
Norway
Akershus University Hospital Oslo 3 3 0 37
Stavanger Universitetssjukehus Stavanger 1 1 0 75
Universitetssykehuset Nord-Norge Tromsö Tromsø 5 5 0 25
Ålesund Sjukehus Ålesund 1 1 0 129
Sörlandet Sykehus Kristiansand Kristiansand 1 1 0 121
Sykehuset Östfold Kalnes Østfold 3 3 0 59
Sweden
Capio Saint Göran's Hospital Stockholm 2 2 0 74
Karolinska Universitetssjukhuset Stockholm 5 5 0 32
Norrlands Universitetssjukhus Umeå 1 1 0 173
Länssjukhuset i Sundsvall Sundsvall 3 3 0 81
Växjö lasarett Växjö 1 1 0 123
Switzerland
University Hospital Basel Basel 4 4 0 87
St. Claraspital Basel 1 1 0 104
Kantonspital Aarau Aarau 2 2 0 40

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 0 262
UZ Gent Ghent 40 22 10 18 0 360
AZ Groeninge Kortrijk 13 7 4 6 0 384
OLV Aalst Aalst 24 9 1 15 0 255
AZ Damiaan Ostend 6 3 0 3 0 312
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 9 7 5 2 0 814
AZ St-Lucas Brugge AZ Sint-Lucas 6 2 0 4 0 993
CHU Liège Liège 18 14 7 4 0 347
Jessa Ziekenhuis Hasselt 2 2 1 0 0 1067
AZ Nikolaas Sint-Niklaas 13 7 2 6 0 396
GZA Sint-Augustinus Antwerp 30 18 4 12 0 355
Helora Hospital La Louviere Site Jolimont La Louvière 3 1 0 2 0 369
Norway
Akershus University Hospital Akershus University Hospital 28 11 6 17 0 241
Stavanger Universitetssjukehus Stavanger 50 25 9 25 0 230
Universitetssykehuset Nord-Norge Tromsö Tromsø 11 7 0 4 0 493
Ålesund Sjukehus Ålesund 12 4 2 8 0 324
Sörlandet Sykehus Kristiansand Kristiansand 7 6 1 1 0 276
Sykehuset Östfold Kalnes Norway 3 2 0 1 0 187
Sweden
Capio Saint Göran's Hospital Stockholm 63 38 15 25 0 269
Karolinska Universitetssjukhuset Stockholm 39 25 13 14 0 457
Akademiska Sjukhuset Uppsala 35 22 10 13 0 346
Norrlands Universitetssjukhus Umeå 24 17 7 7 0 318
Länssjukhuset i Sundsvall Sundsvall 31 21 7 10 0 305
Länssjukhuset i Ryhov Jönköping 40 26 15 14 0 453
Växjö lasarett Sweden 19 11 5 8 0 346
Länssjukhuset i Karlstad Karlstad 23 13 8 10 0 551
Länssjukhuset i Kalmar Kalmar 9 5 3 4 0 677
Falu lasarett Falun 11 6 1 5 0 425
Södra Älvsborgs sjukhus Borås 8 6 1 2 0 346
Universitetssjukhuset Örebro Örebro 4 2 1 2 0 291
Switzerland
University Hospital Basel Basel 12 9 1 3 0 486
St. Claraspital Basel 4 1 0 3 0 474

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.