This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04015622
Recruitment Status : Recruiting
First Posted : July 11, 2019
Last Update Posted : September 21, 2023
Sponsor:
Information provided by (Responsible Party):
British Columbia Cancer Agency

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostate Cancer (mCRPC) Drug: Enzalutamide Drug: Docetaxel Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 7, 2020
Estimated Primary Completion Date : April 1, 2025
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: Xtandi

Drug: Docetaxel
Docetaxel 75 mg/m2 IV every 3 weeks
Other Name: 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 Name: Xtandi

Drug: Docetaxel
Docetaxel 75 mg/m2 IV every 3 weeks
Other Name: Taxotere


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. Correlation of specific ctDNA-based genomic alterations to treatment response [ Time Frame: 1 year ]
    Among mCRPC patients receiving enzalutamide and docetaxel


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT04015622


Contacts
Layout table for location contacts
Contact: Kim N Chi, MD 6048776000 ext 672734 kchi@bccancer.bc.ca
Contact: Daniel Khalaf, MD 6048776000 ext 672418 daniel.khalaf@bccancer.bc.ca

Locations
Layout table for location information
Canada, British Columbia
BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre) Recruiting
Kelowna, British Columbia, Canada, V1Y 5L3
Contact: Daygen Finch, MD    2507123900    DFinch-02@bccancer.bc.ca   
Principal Investigator: Daygen Finch, MD         
BC Cancer - Surrey Centre Recruiting
Surrey, British Columbia, Canada, V3V 1Z2
Contact: Krista Noonan, MD    6049304064    KNoonan2@bccancer.bc.ca   
Principal Investigator: Krista Noonan, MD         
BC Cancer - Vancouver Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Kim N Chi, MD    6048776000 ext 672734    kchi@bccancer.bc.ca   
Principal Investigator: Kim N. Chi, MD         
BC Cancer - Victoria Centre Recruiting
Victoria, British Columbia, Canada, V8R 6V5
Contact: Joanna Vergidis, MD    2505195572    JVergidis@bccancer.bc.ca   
Principal Investigator: Joanna Vergidis, MD         
Sponsors and Collaborators
British Columbia Cancer Agency
Investigators
Layout table for investigator information
Study Chair: Kim N Chi, MD British Columbia Cancer Agency
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:
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. Erratum In: Cell. 2015 Jul 16;162(2):454.
Khalaf D, Annala M, Finch DL, et al. Phase 2 randomized cross-over trial of abiraterone + prednisone (ABI+P) vs enzalutamide (ENZ) for patients (pts) with metastatic castration resistant prostate cancer (mCPRC): Results for 2nd-line therapy. J Clin Oncol [Internet] 2018;36(15_suppl):5015.

Layout table for additonal information
Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT04015622    
Other Study ID Numbers: PROTRACT
First Posted: July 11, 2019    Key Record Dates
Last Update Posted: September 21, 2023
Last Verified: September 2023

Layout table for additional information
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
Keywords provided by British Columbia Cancer Agency:
circulating tumor DNA
Enzalutamide
Docetaxel
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
 Prostatic Diseases
Male Urogenital Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action