RecruitingPhase 3NCT03903835

ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer

ProBio: An Outcome-adaptive and Randomized Multi-arm Biomarker Driven Study in Patients With Metastatic Prostate Cancer


Sponsor

Karolinska Institutet

Enrollment

750 participants

Start Date

Feb 1, 2019

Study Type

INTERVENTIONAL

Conditions

Summary

ProBio is an international, outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic 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 inferred from diagnostic tissue or liquid biopsy profiling. The predefined biomarker signatures are tumor properties or mutations in genes/pathways with previously demonstrated clinical validity (e.g. prognostic value or association with treatment response). The biomarker signatures are identified using a hybridisation capture gene panel specifically designed for prostate cancer.


Eligibility

Sex: MALEMin Age: 18 Years

Inclusion Criteria7

  • Man with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing newly diagnosed (i.e. de novo) hormone sensitive prostate cancer (mHSPC) or first-line castration resistant prostate cancer (mCRPC)
  • Distant metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI
  • Adequate health as assessed by the investigator to receive all available treatments in the trial
  • ECOG/WHO (Eastern Cooperative Oncology Group/ World Health Organization) performance score 0-2
  • Adequate organ and bone marrow function
  • Albumin greater than or equal to 28 g/L
  • Able to understand the patient information and sign written informed consent

Exclusion Criteria11

  • Other malignancies within 5 years except non-melanoma skin cancer
  • Within 6 months of randomization: myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, TIA (transient ischemic attack), or congestive heart failure NYHA (New York Heart Association) class III or IV
  • Uncontrolled hypertension
  • Uncontrolled hypotension
  • Received systemic therapy (with the exception of standard ADT) prior to study inclusion, for the CRPC indication
  • Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results
  • Unable to comply with study procedures
  • Current participation in another clinical trial that will be in conflict with the present study, administration of an investigational therapeutic or invasive surgical procedure within 28 days prior to study enrolment
  • Patients who are unlikely to comply with the protocol
  • Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subjects participation in this study.
  • Any medical condition that would make use of the study treatments contraindicated, according to the SmPC, e.g. significant heart or liver disease.

Interventions

DRUGEnzalutamide Oral Capsule

Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).

DRUGAbiraterone Oral Tablet

Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

DRUGCarboplatin

Carboplatin will be administered every 3rd week with an AUC (area under curve) = 5 with a dose calculated according to the Carboplatin AUC Dose calculation (Calvert formula):Dose (mg) = TargetAUC (mg/ml x min) x \[GFR ml/min + 25\].

DRUGCabazitaxel 60 mg Solution for Injection

Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

DRUGDocetaxel Injectable Solution

Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

DRUGRadium Chloride Ra-223

Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

DRUGNiraparib plus Abiraterone acetate plus Prednisone

Niraparib and Abiraterone acetate will be provided by Janssen and will be provided either as a fixed dose combination or as single agents. Detailed use of the study treatment including dose and dosages are described in the Investigator's brochures and SmPC.

DRUGCapivasertib plus Docetaxel

Capivasertib is provided by AstraZeneca and will be given in combination with Docetaxel. All subjects will be given up to ten 21-day docetaxel cycles. All subjects will receive Capivasertib, which will be administered as tablets taken twice a day orally, on a 4 days on/3 days off continuous schedule, commencing cycle one, day 2, until disease progression.

DRUGApalutamide

Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).

DRUGDarolutamide

Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).


Locations(32)

OLV Ziekenhuis Aalst

Aalst, Belgium

GZA Sint-Augustinus

Antwerp, Belgium

AZ Sint-Jan AV

Bruges, Belgium

AZ Sint-Lucas

Bruges, Belgium

Ziekenhuis Oost-Limburg

Genk, Belgium

University Hospital Ghent

Ghent, Belgium

AZ Jan Palfijn Ziekenhuis

Ghent, Belgium

Jessa ziekenhuis

Hasselt, Belgium

AZ Groeninge

Kortrijk, Belgium

University Hospital Luik

Liège, Belgium

AZ Damiaan

Ostend, Belgium

VITAZ

Sint-Niklaas, Belgium

Ålesund Sjukehus

Ålesund, Norway

Kreftsenter Kristiansand

Kristiansand, Norway

Akershus Universitetssykehus

Lørenskog, Norway

Stavanger Universitetssjukehus

Stavanger, Norway

Universitetssykehuset Nord-Norge Tromsö

Tromsø, Norway

Falu lasarett

Falun, Region Dalarna, Sweden

Södra Alvsborgs sjukhus

Borås, Sweden

Länssjukhuset Ryhov - Onkologiska kliniken

Jönköping, Sweden

Länssjukhuset

Kalmar, Sweden

Centralsjukhuset Region Värmland

Karlstad, Sweden

Universitetssjukhuset Örebro

Örebro, Sweden

Karolinska University Hospital

Stockholm, Sweden

Capio St.Görans Hospital

Stockholm, Sweden

Länssjukhuset Sundsvall Härnösand

Sundsvall, Sweden

Norrlands Universitetssjukhus

Umeå, Sweden

Akademiska sjukhuset

Uppsala, Sweden

Hallands sjukhus Varberg

Varberg, Sweden

Centrallasarettet Onkologkliniken

Vaxjo, Sweden

St. Claraspital

Basel, Switzerland

Universitätsspital Basel

Basel, Switzerland

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NCT03903835


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