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Metastatic Castration-Resistant Prostate Cancer (mCRPC)Phase 2PROTRACTNCT04015622

PROstate Cancer TReatment Optimization Via Analysis of Circulating Tumour DNA

A Phase 2 study testing Enzalutamide and Docetaxel in people with Metastatic Castration-Resistant Prostate Cancer (mCRPC), run by British Columbia Cancer Agency at 7 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Enzalutamide and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
7 sitesCanada
Study dates
7 Oct 2020to 30 Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet ALL of the following criteria:
  • Willing and able to provide informed consent
  • Adult males ≥ 18 years age
  • 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
  • Consent to analysis of archival tissue collected at diagnosis is mandatory
  • 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)
Show all 21Show fewer
  • Evidence of metastatic disease on bone scan or CT scan
  • 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:
  • 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
  • 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).
  • Bone progression: ≥ 2 new lesions on bone scan confirmed on subsequent bone scan at least 8 weeks apart (2+2 rule as per PCWG317)
  • ECOG performance status 0-2 (see Appendix C)
  • Prior treatment with abiraterone, in either castration-sensitive or castration-resistant setting.
  • Eligible for treatment with either enzalutamide or docetaxel as per standard of care guidelines
  • Adequate organ function defined as:
  • Absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L and hemoglobin ≥ 90 g/L
  • Creatinine clearance ≥ 30 ml/min (calculated by Cockcroft-Gault formula, see Appendix D)
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)
  • Alanine aminotransferase (ALT) ≤ 5 x ULN
  • Able to swallow study drug and comply with study requirements including provision of peripheral blood samples at specified time points for correlative studies
  • Recovery from all prior treatment-related toxicity to grade ≤ 2 (as per CTCAE 5.0)

Who cannot join

  • Patients must NOT meet any of the following criteria:
  • Severe concurrent illness or co-morbid disease that would make the subject unsuitable for enrolment
  • Prior therapy with enzalutamide or other experimental anti-androgens (e.g. ARN-509, TOK-001)
  • 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)
  • 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)
  • 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)
Show all 12Show fewer
  • Brain metastases or active epidural disease (treated epidural disease is permitted)
  • Contraindication to prednisone therapy including poorly controlled diabetes mellitus
  • History of seizure or seizure disorder, or history of any cerebrovascular event within 6 months of study entry.
  • Uncontrolled hypertension Grade ≥3 (i.e. systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg)
  • Gastrointestinal disorder affecting absorption
  • Major surgery within 4 weeks of starting study treatment

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Canada7 sites

  • BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)

    Kelowna, British Columbia, V1Y 5L3

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • BC Cancer - Centre for the North

    Prince George, British Columbia, V2M 7E9

  • BC Cancer - Surrey Centre

    Surrey, British Columbia, V3V 1Z2

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • BC Cancer - Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

  • BC Cancer - Victoria Centre

    Victoria, British Columbia, V8R 6V5

Other trials in Canada

About this study

Official title: 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.

Read the 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).

Being tested
Enzalutamide, Docetaxel
Keywords
circulating tumor DNA, Enzalutamide, Docetaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnzalutamideDrug

    Also called Xtandi

    Enzalutamide 160 mg PO OD

  • DocetaxelDrug

    Also called Taxotere

    Docetaxel 75 mg/m2 IV every 3 weeks

Study groups in NCT04015622
Study groupRoleWhat they receive
A: Biomarker directed Therapy (BT)ExperimentalctDNA 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).
Receives: Drug: Enzalutamide; Drug: Docetaxel
B: Clinician's Choice (CC)Active comparatorEnzalutamide or docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).
Receives: Drug: Enzalutamide; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    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

    Measured: 1 year

Secondary outcomes (6)

  1. Objective response

    To determine the objective response as per RECIST 1.1 in patients treated with biomarker directed therapy vs. clinician's choice.

    Measured: 1 year

  2. PSA response rate

    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.

    Measured: 1 year

  3. Second progression free survival (PFS2)

    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.

    Measured: 1 year

  4. Overall survival (OS)

    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.

    Measured: 2 years

  5. Clinical benefit rate (CBR)

    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).

    Measured: 3 months

  6. Correlation of specific ctDNA-based genomic alterations to treatment response

    Among mCRPC patients receiving enzalutamide and docetaxel

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2019
  2. Study start7 Oct 2020
  3. Primary completion31 Jan 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04015622
Sponsor's protocol ID
PROTRACT
Acronym
PROTRACT
Status last verified
Oct 2026
First submitted
9 Jul 2019
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Ozguroglu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017 Jul 27;377(4):352-360. doi: 10.1056/NEJMoa1704174. Epub 2017 Jun 4.

    PubMed 28578607

  • James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, Matheson D, Millman R, Attard G, Chowdhury S, Cross WR, Gillessen S, Parker CC, Russell JM, Berthold DR, Brawley C, Adab F, Aung S, Birtle AJ, Bowen J, Brock S, Chakraborti P, Ferguson C, Gale J, Gray E, Hingorani M, Hoskin PJ, Lester JF, Malik ZI, McKinna F, McPhail N, Money-Kyrle J, O'Sullivan J, Parikh O, Protheroe A, Robinson A, Srihari NN, Thomas C, Wagstaff J, Wylie J, Zarkar A, Parmar MKB, Sydes MR; STAMPEDE Investigators. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017 Jul 27;377(4):338-351. doi: 10.1056/NEJMoa1702900. Epub 2017 Jun 3.

    PubMed 28578639

  • Attard G, Parker C, Eeles RA, Schroder F, Tomlins SA, Tannock I, Drake CG, de Bono JS. Prostate cancer. Lancet. 2016 Jan 2;387(10013):70-82. doi: 10.1016/S0140-6736(14)61947-4. Epub 2015 Jun 11.

    PubMed 26074382

  • Lorente D, Mateo J, Perez-Lopez R, de Bono JS, Attard G. Sequencing of agents in castration-resistant prostate cancer. Lancet Oncol. 2015 Jun;16(6):e279-92. doi: 10.1016/S1470-2045(15)70033-1. Epub 2015 May 27.

    PubMed 26065613

  • Wyatt AW, Gleave ME. Targeting the adaptive molecular landscape of castration-resistant prostate cancer. EMBO Mol Med. 2015 Jul;7(7):878-94. doi: 10.15252/emmm.201303701.

    PubMed 25896606

  • Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng FY, Tomlins SA, Cooney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, Reuter VE, Gopalan A, Gao J, Loda M, Lis RT, Bowden M, Balk SP, Gaviola G, Sougnez C, Gupta M, Yu EY, Mostaghel EA, Cheng HH, Mulcahy H, True LD, Plymate SR, Dvinge H, Ferraldeschi R, Flohr P, Miranda S, Zafeiriou Z, Tunariu N, Mateo J, Perez-Lopez R, Demichelis F, Robinson BD, Schiffman M, Nanus DM, Tagawa ST, Sigaras A, Eng KW, Elemento O, Sboner A, Heath EI, Scher HI, Pienta KJ, Kantoff P, de Bono JS, Rubin MA, Nelson PS, Garraway LA, Sawyers CL, Chinnaiyan AM. Integrative clinical genomics of advanced prostate cancer. Cell. 2015 May 21;161(5):1215-1228. doi: 10.1016/j.cell.2015.05.001.

    PubMed 26000489

  • Chedgy EC, Annala M, Beja K, Warner EW, Gleave ME, Chi KN, Wyatt AW. Moving Toward Personalized Care: Liquid Biopsy Predicts Response to Cisplatin in an Unusual Case of BRCA2-Null Neuroendocrine Prostate Cancer. Clin Genitourin Cancer. 2016 Apr;14(2):e233-6. doi: 10.1016/j.clgc.2015.12.023. Epub 2015 Dec 24. No abstract available.

    PubMed 26797585

  • Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol. 2016 Jan 26;17:10. doi: 10.1186/s13059-015-0864-1.

    PubMed 26813233

  • Wyatt AW, Azad AA, Volik SV, Annala M, Beja K, McConeghy B, Haegert A, Warner EW, Mo F, Brahmbhatt S, Shukin R, Le Bihan S, Gleave ME, Nykter M, Collins CC, Chi KN. Genomic Alterations in Cell-Free DNA and Enzalutamide Resistance in Castration-Resistant Prostate Cancer. JAMA Oncol. 2016 Dec 1;2(12):1598-1606. doi: 10.1001/jamaoncol.2016.0494.

    PubMed 27148695

  • Azad AA, Volik SV, Wyatt AW, Haegert A, Le Bihan S, Bell RH, Anderson SA, McConeghy B, Shukin R, Bazov J, Youngren J, Paris P, Thomas G, Small EJ, Wang Y, Gleave ME, Collins CC, Chi KN. Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer. Clin Cancer Res. 2015 May 15;21(10):2315-24. doi: 10.1158/1078-0432.CCR-14-2666. Epub 2015 Feb 23.

    PubMed 25712683

  • Annala M, Struss WJ, Warner EW, Beja K, Vandekerkhove G, Wong A, Khalaf D, Seppala IL, So A, Lo G, Aggarwal R, Small EJ, Nykter M, Gleave ME, Chi KN, Wyatt AW. Treatment Outcomes and Tumor Loss of Heterozygosity in Germline DNA Repair-deficient Prostate Cancer. Eur Urol. 2017 Jul;72(1):34-42. doi: 10.1016/j.eururo.2017.02.023. Epub 2017 Mar 1.

    PubMed 28259476

  • Quigley D, Alumkal JJ, Wyatt AW, Kothari V, Foye A, Lloyd P, Aggarwal R, Kim W, Lu E, Schwartzman J, Beja K, Annala M, Das R, Diolaiti M, Pritchard C, Thomas G, Tomlins S, Knudsen K, Lord CJ, Ryan C, Youngren J, Beer TM, Ashworth A, Small EJ, Feng FY. Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors. Cancer Discov. 2017 Sep;7(9):999-1005. doi: 10.1158/2159-8290.CD-17-0146. Epub 2017 Apr 27.

    PubMed 28450426

  • Wyatt AW, Annala M, Aggarwal R, Beja K, Feng F, Youngren J, Foye A, Lloyd P, Nykter M, Beer TM, Alumkal JJ, Thomas GV, Reiter RE, Rettig MB, Evans CP, Gao AC, Chi KN, Small EJ, Gleave ME. Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer. J Natl Cancer Inst. 2017 Dec 1;109(12):djx118. doi: 10.1093/jnci/djx118.

    PubMed 29206995

  • Annala M, Vandekerkhove G, Khalaf D, Taavitsainen S, Beja K, Warner EW, Sunderland K, Kollmannsberger C, Eigl BJ, Finch D, Oja CD, Vergidis J, Zulfiqar M, Azad AA, Nykter M, Gleave ME, Wyatt AW, Chi KN. Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer. Cancer Discov. 2018 Apr;8(4):444-457. doi: 10.1158/2159-8290.CD-17-0937. Epub 2018 Jan 24.

    PubMed 29367197

  • Beltran H, Wyatt AW, Chedgy EC, Donoghue A, Annala M, Warner EW, Beja K, Sigouros M, Mo F, Fazli L, Collins CC, Eastham J, Morris M, Taplin ME, Sboner A, Halabi S, Gleave ME. Impact of Therapy on Genomics and Transcriptomics in High-Risk Prostate Cancer Treated with Neoadjuvant Docetaxel and Androgen Deprivation Therapy. Clin Cancer Res. 2017 Nov 15;23(22):6802-6811. doi: 10.1158/1078-0432.CCR-17-1034. Epub 2017 Aug 25.

    PubMed 28842510

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide and Docetaxel in people with Metastatic Castration-Resistant Prostate Cancer (mCRPC), run by British Columbia Cancer Agency at 7 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04015622, which also lists 55 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

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