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ProBio: A Biomarker Driven Study in Patients With Metastatic Castrate Resistant Prostate Cancer (ProBio)

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ClinicalTrials.gov Identifier: NCT03903835
Recruitment Status : Recruiting
First Posted : April 4, 2019
Last Update Posted : June 26, 2019
Sponsor:
Collaborator:
The Swedish Research Council
Information provided by (Responsible Party):
Henrik Grönberg, Karolinska Institutet

Brief Summary:

Metastatic castrate resistant prostate cancer (mCRPC) is an advanced form of prostate cancer that affects 2500 - 3000 Swedish men every year. 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 hospitals.


Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostatic Cancer Drug: Enzalutamide Oral Capsule [Xtandi] Drug: Abiraterone Oral Tablet [Zytiga] Drug: Carboplatin Drug: Cabazitaxel 60 mg Solution for Injection Drug: Docetaxel Injectable Solution Drug: Radium Chloride Ra-223 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: ProBio will use outcome-adaptive randomization, adapting the randomization based on the observed 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 analysed within a Bayesian framework, which allows for calculations of the probability for each treatment that 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ProBio: An Outcome-adaptive and Randomized Multi-arm Biomarker Driven Study in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Active Comparator: Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
Drug: Enzalutamide Oral Capsule [Xtandi]
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).

Drug: Abiraterone Oral Tablet [Zytiga]
Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

Drug: Cabazitaxel 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.

Drug: Docetaxel 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.

Drug: Radium 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.

Experimental: Treatment 1: Enzalutamide
Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment of Abiraterone or Enzalutamide.
Drug: Enzalutamide Oral Capsule [Xtandi]
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).

Experimental: Treatment 2: Abiraterone
Patients with an intact androgen receptor (AR) and without TP53 mutations will have an increased chance of being randomised to treatment of Abiraterone or Enzalutamide.
Drug: Abiraterone Oral Tablet [Zytiga]
Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

Experimental: Treatment 3: Carboplatin
DNA-repair deficient patients will have an increased chance of receiving Carboplatin.
Drug: Carboplatin
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].

Experimental: Treatment 4: Cabazitaxel
Patients with the TMPRSS2-ERG gene fusion will have increased chance of receiving chemotherapy at study onset.
Drug: Cabazitaxel 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.

Experimental: Treatment 5: Docetaxel
Patients with the TMPRSS2-ERG gene fusion will have increased chance of receiving chemotherapy at study onset.
Drug: Docetaxel 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.




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Until progressive disease or 36 months from start of treatment, whatever occurs first. ]
    Progression will be evaluated by the established international standards of the Prostate Cancer Working Group version 3 (PCWG3) and for soft tissue metastases (e.g. lung, liver and lymph nodes) according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1).


Secondary Outcome Measures :
  1. Treatment response rate [ Time Frame: 4 months after treatment start ]
    Treatment response is evaluated according to PCWG3 and RECIST 1.1

  2. Overall survival (OS) [ Time Frame: From enrolment to completion of study (60 months) ]
    OS is defined as time to death from any cause (overall and prostate cancer specific)

  3. Patient Reported Outcome Measures (PROM) [ Time Frame: From enrolment to completion of study (60 months) ]
    QoL will be assessed using a modified EORTC QLQ-C30 instrument

  4. Cost-effectiveness [ Time Frame: From enrolment to completion of study (60 months) ]
    Cost effectiveness will be assessed by using the EQ-5D-5L instrument to estimate health utilities. Treatment costs will be based on drug costs and reimbursement data.

  5. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From enrolment to completion of study (60 months) ]
    Common Terminology Criteria for Adverse Events (CTCAE) developed and maintained by the US National Cancer Institute will be used to record adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Man with metastatic castrate resistant prostate cancer (histologically confirmed prostate adenocarcinoma) and castrate levels < 50 ng/dl of serum
  • 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 umol/L
  • Able to understand the patient information and sign written informed consent

Exclusion Criteria:

  • 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
  • Received more than two of the study treatments included in the ProBio study, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03903835


Contacts
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Contact: Berit Larsson, MSc +46 8 52482576 berit.larsson@ki.se
Contact: Henrik Grönberg, Professor +46 70 3411356 Henrik.gronberg@ki.se

Locations
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Sweden
Karolinska University Hospital Recruiting
Stockholm, Sweden, 17176
Contact: Berit Larsson, MSc       berit.larsson@ki.se   
Principal Investigator: Anders Ullén, MD, PhD         
Capio St.Görans Hospital Recruiting
Stockholm, Sweden
Contact: Henrik Grönberg, Professor       henrik.gronberg@capiostgoran.se   
Contact: Marie Hjälm Eriksson, MD PhD       Marie.Hjalm-Eriksson@capiostgoran.se   
Länssjukhuset Sundsvall Härnösand Recruiting
Sundsvall, Sweden, 851 86
Contact: Berit Larsson, MSc       berit.larsson@ki.se   
Principal Investigator: Elin Jänes, MD PhD         
Norrlands Universitetssjukhus Not yet recruiting
Umeå, Sweden, 90185
Contact: Berit Larsson, MSc       berit.larsson@ki.se   
Principal Investigator: Camilla Thellenberg Karlsson, MD PhD         
Akademiska sjukhuset Recruiting
Uppsala, Sweden, 75185
Contact: Berit Larsson, MSc       berit.larsson@ki.se   
Principal Investigator: Lennart Åström, MD PhD         
Sponsors and Collaborators
Henrik Grönberg
The Swedish Research Council
Investigators
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Principal Investigator: Henrik Grönberg, Professor Karolinska Institutet
Study Director: Martin Eklund, PhD Karolinska Institutet
Study Director: Johan Lindberg, PhD Karolinska Institutet

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Responsible Party: Henrik Grönberg, Professor of Cancer Epidemiology, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03903835     History of Changes
Other Study ID Numbers: EudraCT No 2018-002350-78
First Posted: April 4, 2019    Key Record Dates
Last Update Posted: June 26, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carboplatin
Docetaxel
Radium Ra 223 dichloride
Pharmaceutical Solutions
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action