PROstate Cancer TReatment Optimization Via Analysis of Circulating Tumour DNA (PROTRACT)

August 15, 2025 updated by: British Columbia Cancer Agency

A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone

The purpose of this study is to assess the strategy in treatment selection using ctDNA fraction as a predictive biomarker to direct treatment decision (ctDNA fraction <2% receives enzalutamide, and ctDNA fraction ≥2% receives docetaxel) versus clinician's choice of enzalutamide or docetaxel, in subjects with metastatic castration-resistant prostate cancer post abiraterone setting.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, open-label, phase II trial with 1:1 randomization to either Arm A biomarker directed therapy (patients with ctDNA fraction <2% receive enzalutamide, and ctDNA fraction ≥2% receive docetaxel), versus Arm B clinician's choice of enzalutamide or docetaxel, in subjects with metastatic castration-resistant prostate cancer post abiraterone. At time of progression, patient will cross-over to the other therapy (e.g., enzalutamide to docetaxel, and docetaxel to enzalutamide).

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)
      • Prince George, British Columbia, Canada, V2M 7E9
        • BC Cancer - Centre for the North
      • Surrey, British Columbia, Canada, V3V 1Z2
        • BC Cancer - Surrey Centre
      • Toronto, British Columbia, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer - Vancouver Centre
      • Victoria, British Columbia, Canada, V8R 6V5
        • BC Cancer - Victoria Centre
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • London Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

Patients must meet ALL of the following criteria:

  1. Willing and able to provide informed consent
  2. Adult males ≥ 18 years age
  3. History of histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine or small cell differentiation. If histology is not available, patients must have metastatic disease typical of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes) AND a serum concentration of PSA that is rising and >20ng/mL at the time prostate cancer was diagnosed clinically
  4. Consent to analysis of archival tissue collected at diagnosis is mandatory
  5. Prior surgical orchiectomy or if on LHRH agonist/antagonist then testosterone < 1.7 nmol/L at screening visit (patients must maintain LHRH agonist/antagonist therapy for duration of study treatment if not surgically castrated)
  6. Evidence of metastatic disease on bone scan or CT scan

  7. Evidence of biochemical or imaging progression in the setting of surgical or medical castration while on abiraterone. Progressive disease for study entry is defined by one of the following three criteria as per PCWG317:

    1. PSA progression: minimum of two rising PSA values from a baseline measurement of one week interval. Minimum PSA at screening visit is 1.0 ng/mL
    2. Soft tissue or visceral disease progression: an increase ≥20% in the sum of the diameter (short axis for nodal lesions and long axis for non-nodal lesions) from the smallest sum of the diameter since treatment started, or appearance of any new lesions (see Appendix B for definition of measurable disease as per RECIST 1.1 criteria).
    3. Bone progression: ≥ 2 new lesions on bone scan confirmed on subsequent bone scan at least 8 weeks apart (2+2 rule as per PCWG317)
  8. ECOG performance status 0-2 (see Appendix C)
  9. Prior treatment with abiraterone, in either castration-sensitive or castration-resistant setting.
  10. Eligible for treatment with either enzalutamide or docetaxel as per standard of care guidelines

  11. Adequate organ function defined as:

    1. Absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L and hemoglobin ≥ 90 g/L
    2. Creatinine clearance ≥ 30 ml/min (calculated by Cockcroft-Gault formula, see Appendix D)
    3. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)
    4. Alanine aminotransferase (ALT) ≤ 5 x ULN
  12. Able to swallow study drug and comply with study requirements including provision of peripheral blood samples at specified time points for correlative studies
  13. Recovery from all prior treatment-related toxicity to grade ≤ 2 (as per CTCAE 5.0)

EXCLUSION CRITERIA

Patients must NOT meet any of the following criteria:

  1. Severe concurrent illness or co-morbid disease that would make the subject unsuitable for enrolment
  2. Prior therapy with enzalutamide or other experimental anti-androgens (e.g. ARN-509, TOK-001)
  3. Prior systemic chemotherapy with docetaxel or cabazitaxel (with the exception of: patients who were treated with docetaxel for castration sensitive disease and did not progress for at least 12 months after completion of docetaxel)
  4. Active concurrent malignancy (with the exception of non-melanomatous skin cancer, or other solid tumours curatively treated with no evidence of disease for ≥3 years)
  5. Wide-field radiotherapy or radioisotopes such as Strontium-89, or Radium-223 ≤ 28 days prior to starting study drug (limited-field palliative radiotherapy for up to 5 fractions prior to starting study drug is permitted)
  6. Brain metastases or active epidural disease (treated epidural disease is permitted)
  7. Contraindication to prednisone therapy including poorly controlled diabetes mellitus
  8. History of seizure or seizure disorder, or history of any cerebrovascular event within 6 months of study entry.
  9. Uncontrolled hypertension Grade ≥3 (i.e. systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg)
  10. Gastrointestinal disorder affecting absorption
  11. Major surgery within 4 weeks of starting study treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: Biomarker directed Therapy (BT)
ctDNA fraction <2% receives enzalutamide, and ctDNA fraction ≥2% receives docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).
Drug: Enzalutamide
Enzalutamide 160 mg PO OD
Other Names:
  • Xtandi
Drug: Docetaxel
Docetaxel 75 mg/m2 IV every 3 weeks
Other Names:
  • Taxotere
Active Comparator: B: Clinician's Choice (CC)
Enzalutamide or docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).
Drug: Enzalutamide
Enzalutamide 160 mg PO OD
Other Names:
  • Xtandi
Drug: Docetaxel
Docetaxel 75 mg/m2 IV every 3 weeks
Other Names:
  • Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: 1 year
PFS is defined as the time between the date of starting trial treatment to any of the following: clinical, PSA, radiographic progression, or death from any cause on first-line therapy
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response
Time Frame: 1 year
To determine the objective response as per RECIST 1.1 in patients treated with biomarker directed therapy vs. clinician's choice.
1 year
PSA response rate
Time Frame: 1 year
PSA response rate is defined as the proportion of patients with a PSA decline (defined as a ≥30%, ≥50% and other declines in PSA from baseline) in mCRPC patients treated with biomarker directed therapy vs. clinician's choice.
1 year
Second progression free survival (PFS2)
Time Frame: 1 year
PFS2 is defined as the time elapsed between the date of treatment commencement and the first documented evidence of any disease progression or death from any cause from cross-over second-line therapy.
1 year
Overall survival (OS)
Time Frame: 2 years
OS is defined as time from treatment commencement to death of any cause of mCRPC patients treated with biomarker directed therapy vs. clinician's choice.
2 years
Clinical benefit rate (CBR)
Time Frame: 3 months
CBR is defined as PSA or measurable radiological response of any duration or stable disease for ≥ 12 weeks (no symptomatic progression, PSA progression, or objective disease progression).
3 months
Correlation of specific ctDNA-based genomic alterations to treatment response
Time Frame: 1 year
Among mCRPC patients receiving enzalutamide and docetaxel
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

British Columbia Cancer Agency

Investigators

  • Study Chair: Kim N Chi, MD, British Columbia Cancer Agency

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2020

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

July 9, 2019

First Submitted That Met QC Criteria

July 9, 2019

First Posted (Actual)

July 11, 2019

Study Record Updates

Last Update Posted (Actual)

August 20, 2025

Last Update Submitted That Met QC Criteria

August 15, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROTRACT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Clinical Trials on Enzalutamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Italy

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe