ProBio: A Biomarker Driven Study in Patients With Metastatic Castrate Resistant Prostate Cancer (ProBio)
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- STATUS
- Recruiting
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- End date
- Dec 23, 2026
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- participants needed
- 750
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- sponsor
- Karolinska Institutet
Summary
Metastatic castrate resistant prostate cancer (mCRPC) is an advanced form of prostate cancer and it is estimated that around 20-30% of all prostate cancer diagnoses will develop mCRPC at some point in their disease trajectory. The last years, new drugs have been approved for treatment of mCRPC. Although the drugs are beneficial for many patients they carry three serious disadvantages: treatment costs are high, the response rates are low and there are no predictive treatment markers available in clinical care today. There are promising research that linked changes in the tumor's genome with better or worse response to drug treatment.The purpose of the ProBio study is to investigate whether profiling of the tumor's genome can be used to select a treatment that is highly likely to produce good effect. In order to investigate the tumor cells' genome we will use a biomarker in blood, so-called circulating tumor DNA.
Our hypothesis is that one can significantly prolong progression-free survival compared to current clinical practice by measuring free circulating tumor DNA in plasma and adapting the treatment accordingly.
In this way, treatment can be tailored, which leads to benefits for both patient and health care.
The hypothesis will be tested in a large clinical study with 750 patients diagnosed with CRPC. Recruitment to the clinical treatment study will take place at a number of Swedish and Belgian hospitals, and the study will be expanded to sites in Norway and Switzerland.
Description
ProBio is an outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic castrate resistant prostate cancer.
Patients will be randomized to control or experimental treatment arms. Patients in the control arm will receive standard of care following national guidelines. Patients in the experimental arm will be randomized to treatments based on a biomarker signature. The biomarker signatures are defined as tumor properties or mutations in certain genes/pathways identified in the scientific literature as important in prostate cancer treatment response. The biomarker signatures are identified using a circulating tumor DNA (ctDNA) panel specifically designed for mCRPC.
Alterations in the following genes/pathways or combinations thereof constitute the biomarker
- signatures
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- Androgen receptor
- DNA-repair deficiency
- TP53
- TMPRSS2-ERG gene fusion
Patients in the experimental arm can be randomized to the following treatments:
- Enzalutamide
- Abiraterone
- Cabazitaxel
- Docetaxel
- Carboplatin
- Niraparib plus Abiraterone acetate plus Prednisone
ProBio will use outcome-adaptive randomization, adapting the randomization based on the observed progression free survival (PFS) within biomarker signatures. Treatments will initially be assigned to patients based on the biomarker signatures for which that treatment is most likely to be effective. The trial will be analyzed within a Bayesian framework, which allows for calculations of the probability for each treatment that it is superior to standard of care within a given signature. Each experimental arm will be evaluated for efficacy relative to the control arm with the same biomarker signatures.
Participants and treating physicians will be blinded to ctDNA profile of each patient. The biomarker signatures will thus not influence treatment choice among controls (reflecting today's standard of care).
Further, ProBio will use the sequential multiple assignments trial (SMART) concept, where each patient who progresses within the trial will re-enter the trial and be re-assigned to another treatment based on the patient's current ctDNA profile. Patients will be withdrawn after in total two randomized consecutive treatments after inclusion into the study.
The randomization probabilities within the experimental arm are defined in proportion to the probability that each treatment is superior to standard of care within a given biomarker signature, and therefore change as data accumulates in the trial and knowledge accumulates for what biomarker signatures and specific treatments that are more probable to be effective.
Trial results will be evaluated regularly by an independent data and safety monitoring board (DSMB). The DSMB will evaluate treatment-signature combinations with respect to:
Graduation for superiority: A treatment-biomarker signature combination will be graduated from the trial if it has a Bayesian predictive probability of success in a future confirmatory phase III trial exceeding a pre-specified threshold (85%).
Termination for futility: Treatment-biomarker signature combinations will be dropped from the trial for futility when success probabilities drop sufficiently low (less than 10% using a minimum of 20 patients assigned to the specific treatment-biomarker signature combination). Alternatively, if the maximum sample size of 150 patients assigned to a treatment biomarker signature is reached without graduation for superiority, assignments to that combination will end.
ProBio is a platform study. This means that new treatments and biomarker signatures can be added to the experimental arm in the future. This will be done after protocol amendments.
Details
| Condition | Metastatic Castration-Resistant Prostatic Cancer |
|---|---|
| Treatment | carboplatin, Enzalutamide Oral Capsule [Xtandi], Abiraterone Oral Tablet [Zytiga], Cabazitaxel 60 mg Solution for Injection, Docetaxel Injectable Solution, Radium Chloride Ra-223, Niraparib plus Abiraterone acetate plus Prednisone |
| Clinical Study Identifier | NCT03903835 |
| Sponsor | Karolinska Institutet |
| Last Modified on | 7 October 2022 |
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