ProBio Trial Progress Portal

Last updated: November 15, 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, 15
DATA CUTOFF DATE: 2025 November, 14
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 111 76 35 0 22
Länssjukhuset i Sundsvall Sundsvall 55 40 15 0 45
Karolinska Universitetssjukhuset Stockholm 54 37 16 1 1
Akademiska Sjukhuset Uppsala 48 28 19 1 2
Länssjukhuset i Ryhov Jönköping 45 30 15 0 95
Norrlands Universitetssjukhus Umeå 37 24 13 0 54
Växjö lasarett Sweden 24 14 10 0 87
Länssjukhuset i Kalmar Kalmar 24 12 9 3 4
Länssjukhuset i Karlstad Karlstad 23 13 10 0 514
Falu lasarett Falun 12 7 5 0 31
Södra Älvsborgs sjukhus Borås 8 6 2 0 309
Universitetssjukhuset Örebro Örebro 4 2 2 0 248
Norway
Stavanger Universitetssjukehus Stavanger 89 52 35 2 11
Akershus University Hospital Akershus University Hospital 55 27 26 2 1
Sörlandet Sykehus Kristiansand Kristiansand 30 20 8 2 2
Universitetssykehuset Nord-Norge Tromsö Tromsø 21 15 6 0 12
Sykehuset Östfold Kalnes Norway 20 13 6 1 4
Ålesund Sjukehus Ålesund 18 7 11 0 92
Belgium
GZA Sint-Augustinus Antwerp 77 49 26 2 3
UZ Gent Ghent 56 31 23 2 2
AZ St-Jan Brugge Bruges 51 30 20 1 3
AZ Groeninge Kortrijk 43 29 13 1 8
CHU Liège Liège 41 30 11 0 40
OLV Aalst Aalst 34 14 19 1 10
AZ Nikolaas Sint-Niklaas 32 20 11 1 9
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 25 19 6 0 26
Helora Hospital La Louviere Site Jolimont La Louvière 17 7 9 1 22
AZ Damiaan Ostend 15 8 7 0 276
AZ St-Lucas Brugge AZ Sint-Lucas 9 2 7 0 695
AZ Maria-Middelares Belgium 3 3 0 0 32
Jessa Ziekenhuis Hasselt 2 2 0 0 1012
Switzerland
University Hospital Basel Basel 43 30 13 0 51
St. Claraspital Basel 9 6 3 0 61
Kantonspital Aarau Aarau 2 0 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 9
UZ Gent Ghent 11 5 5 1 16
AZ Groeninge Kortrijk 28 20 7 1 9
OLV Aalst Aalst 7 2 4 1 12
AZ Damiaan Ostend 10 6 4 0 309
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 16 12 4 0 36
AZ St-Lucas Brugge Bruges 3 0 3 0 702
CHU Liège Liège 28 21 7 0 51
AZ Nikolaas Belgium 19 13 5 1 9
GZA Sint-Augustinus Antwerp 44 28 14 2 10
Helora Hospital La Louviere Site Jolimont La Louvière 10 3 7 0 73
AZ Maria-Middelares Belgium 2 2 0 0 72
Norway
Akershus University Hospital Oslo 25 14 9 2 1
Stavanger Universitetssjukehus Norway 38 26 10 2 11
Universitetssykehuset Nord-Norge Tromsö Tromsø 7 5 2 0 12
Ålesund Sjukehus Ålesund 5 2 3 0 207
Sörlandet Sykehus Kristiansand Kristiansand 23 14 7 2 2
Sykehuset Östfold Kalnes Norway 15 8 6 1 4
Sweden
Capio Saint Göran's Hospital Stockholm 48 37 11 0 23
Karolinska Universitetssjukhuset Sweden 12 9 2 1 1
Akademiska Sjukhuset Uppsala 14 7 6 1 5
Norrlands Universitetssjukhus Sweden 12 6 6 0 54
Länssjukhuset i Sundsvall Sundsvall 24 20 4 0 186
Länssjukhuset i Ryhov Jönköping 5 4 1 0 95
Växjö lasarett Sweden 4 2 2 0 240
Länssjukhuset i Kalmar Kalmar 13 7 5 1 4
Falu lasarett Falun 1 1 0 0 31
Switzerland
University Hospital Basel Basel 34 23 11 0 95
St. Claraspital Basel 4 4 0 0 443
Kantonspital Aarau Aarau 1 0 0 1 12

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 71
UZ Gent Ghent 2 2 0 136
AZ Groeninge Belgium 4 4 0 86
OLV Aalst Aalst 3 3 0 86
Ziekenhuis Oost-Limburg Belgium 1 1 0 143
CHU Liège Liège 1 1 0 156
AZ Nikolaas Belgium 1 1 0 26
GZA Sint-Augustinus Antwerp 3 3 0 37
Helora Hospital La Louviere Site Jolimont Jolimont 2 2 0 89
AZ Maria-Middelares Belgium 1 1 0 32
Norway
Akershus University Hospital Oslo 1 1 0 78
Stavanger Universitetssjukehus Stavanger 1 1 0 39
Universitetssykehuset Nord-Norge Tromsö Tromsø 3 3 0 92
Ålesund Sjukehus Ålesund 1 1 0 93
Sörlandet Sykehus Kristiansand Kristiansand 1 1 0 85
Sykehuset Östfold Kalnes Østfold 2 2 0 67
Sweden
Capio Saint Göran's Hospital Stockholm 2 2 0 38
Karolinska Universitetssjukhuset Stockholm 3 3 0 50
Norrlands Universitetssjukhus Umeå 1 1 0 137
Länssjukhuset i Sundsvall Sundsvall 3 3 0 45
Växjö lasarett Växjö 1 1 0 87
Switzerland
University Hospital Basel Basel 4 4 0 51
St. Claraspital Basel 1 1 0 68

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 0 226
UZ Gent Ghent 40 22 10 18 0 324
AZ Groeninge Kortrijk 13 7 4 6 0 348
OLV Aalst Aalst 24 9 1 15 0 219
AZ Damiaan Ostend 6 3 0 3 0 276
Ziekenhuis Oost-Limburg Ziekenhuis Oost-Limburg 9 7 5 2 0 778
AZ St-Lucas Brugge AZ Sint-Lucas 6 2 0 4 0 957
CHU Liège Liège 18 14 7 4 0 311
Jessa Ziekenhuis Hasselt 2 2 1 0 0 1031
AZ Nikolaas Sint-Niklaas 13 7 2 6 0 360
GZA Sint-Augustinus Antwerp 30 18 4 12 0 319
Helora Hospital La Louviere Site Jolimont La Louvière 3 1 0 2 0 333
Norway
Akershus University Hospital Akershus University Hospital 28 11 6 17 0 205
Stavanger Universitetssjukehus Stavanger 50 25 9 25 0 194
Universitetssykehuset Nord-Norge Tromsö Tromsø 11 7 0 4 0 457
Ålesund Sjukehus Ålesund 12 4 2 8 0 288
Sörlandet Sykehus Kristiansand Kristiansand 7 6 1 1 0 240
Sykehuset Östfold Kalnes Norway 3 2 0 1 0 151
Sweden
Capio Saint Göran's Hospital Stockholm 63 38 15 25 0 233
Karolinska Universitetssjukhuset Stockholm 39 25 13 14 0 421
Akademiska Sjukhuset Uppsala 35 22 10 13 0 310
Norrlands Universitetssjukhus Umeå 24 17 7 7 0 282
Länssjukhuset i Sundsvall Sundsvall 31 21 7 10 0 269
Länssjukhuset i Ryhov Jönköping 40 26 15 14 0 417
Växjö lasarett Sweden 19 11 5 8 0 310
Länssjukhuset i Karlstad Karlstad 23 13 8 10 0 515
Länssjukhuset i Kalmar Kalmar 9 5 3 4 0 641
Falu lasarett Falun 11 6 1 5 0 389
Södra Älvsborgs sjukhus Borås 8 6 1 2 0 310
Universitetssjukhuset Örebro Örebro 4 2 1 2 0 255
Switzerland
University Hospital Basel Basel 12 9 1 3 0 450
St. Claraspital Basel 4 1 0 3 0 438

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.