PROstate Cancer TReatment Optimization Via Analysis of Circulating Tumour DNA

NCT04015622 | Active Not Recruiting Phase 2

• 1 other identifier: PROTRACT
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief 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 metastatic castration-resistant prostate cancer post abiraterone setting.

Conditions

Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Keywords

circulating tumor DNA; Enzalutamide; Docetaxel

Outcome Measures

Primary Outcomes (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

  1 year

Secondary Outcomes (6)

• Objective response

  1 year

• PSA response rate

  1 year

• Second progression free survival (PFS2)

  1 year

• Overall survival (OS)

  2 years

• Clinical benefit rate (CBR)

  3 months

Study Arms (2)

A: Biomarker directed Therapy (BT)

EXPERIMENTAL

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; Drug: Docetaxel

B: Clinician's Choice (CC)

ACTIVE COMPARATOR

Enzalutamide or docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).

Drug: Enzalutamide; Drug: Docetaxel

Interventions

Enzalutamide DRUG

Enzalutamide 160 mg PO OD

Also known as: Xtandi

A: Biomarker directed Therapy (BT); B: Clinician's Choice (CC)

Docetaxel DRUG

Docetaxel 75 mg/m2 IV every 3 weeks

Also known as: Taxotere

A: Biomarker directed Therapy (BT); B: Clinician's Choice (CC)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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:

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (7)

BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer - Centre for the North

Prince George, British Columbia, V2M 7E9, Canada

Location

BC Cancer - Surrey Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, British Columbia, M4N 3M5, Canada

Location

BC Cancer - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BC Cancer - Victoria Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

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MeSH Terms

Interventions

enzalutamide; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Kim N Chi, MD

  British Columbia Cancer Agency

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 11, 2019
• Study Start: October 7, 2020
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 20, 2025

Record last verified: 2025-08

Locations

CA (7)