NCT02125357

Brief Summary

This study is being offered to patients who have castrate-resistant (also known as hormone-refractory) prostate cancer. The cancer has metastasized or spread outside the prostate area to other parts of the body. The purpose of this study is to evaluate the effects of sequencing hormonal therapies (abiraterone acetate and enzalutamide) and to assess treatment efficacy of these two agents.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
202

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2014

Longer than P75 for phase_2

Geographic Reach
1 country

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 22, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 29, 2014

Completed
4 months until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 4, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 4, 2020

Completed
Last Updated

August 7, 2020

Status Verified

August 1, 2020

Enrollment Period

5.4 years

First QC Date

April 22, 2014

Last Update Submit

August 6, 2020

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

sequencingabirateroneenzalutamidemetastatic castration-resistant prostate cancerrandomized

Outcome Measures

Primary Outcomes (1)

  • PSA response rate in mCRPC patients with PSA progression on first-line therapy when crossed over to second-line therapy with the opposite agent

    1 year

Secondary Outcomes (1)

  • Potential biomarkers that are associated with treatment efficacy and/ or resistance

    1 year

Other Outcomes (1)

  • PSA response rate in mCRPC patients treated with first-line abiraterone acetate or enzalutamide

    1 year

Study Arms (2)

A - Abiraterone Acetate

OTHER

Abiraterone acetate 1000mg PO OD with prednisone 5mg PO BID or 10mg OD as per standard of care, or until PSA progression then cross-over to Arm B.

Drug: Abiraterone acetate

B - Enzalutamide

OTHER

160mg PO OD as per standard of care, or until PSA progression then cross-over to Arm A.

Drug: Enzalutamide

Interventions

Abiraterone acetateDRUG

Abiraterone acetate 1000mg PO OD with prednisone 5mg PO BID or 10mg OD as per standard of care.

Also known as: Zytiga
A - Abiraterone Acetate
EnzalutamideDRUG

160mg PO OD as per standard of care.

Also known as: Xtandi
B - Enzalutamide

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Willing and able to provide informed consent
  • Adult males ≥ 18 years age
  • History of adenocarcinoma of the prostate diagnosed histologically without evidence of neuroendocrine or small cell differentiation
  • Prior surgical orchiectomy or if on luteinizing hormone-releasing hormone (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. Progressive disease for study entry is defined by one of the following three criteria:
  • PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement. Minimum PSA at screening visit is \> 2.0 ug/L
  • Soft tissue or visceral disease progression (see Appendix B for definition of measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria)
  • Bone progression: ≥ 2 new lesions on bone scan
  • ECOG performance status 0-2 (see Appendix C)
  • Eligible for treatment with either abiraterone acetate or enzalutamide 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 ≥ 80 g/L
  • Creatinine clearance ≥ 30 ml/min (calculated by Cockcroft-Gault formula, see Appendix D)
  • Serum potassium within normal limits
  • +4 more criteria

You may not qualify if:

  • Severe concurrent illness or co-morbid disease that would make the subject unsuitable for enrolment
  • Prior therapy with CYP17 inhibitors (including abiraterone acetate, TAK-700, TOK-001 and ketoconazole), enzalutamide or other experimental anti-androgens (e.g. ARN-509, TOK-001)
  • Prior systemic chemotherapy for mCRPC
  • Life expectancy \< 6 months
  • Active concurrent malignancy (with the exception of non-melanomatous skin cancer)
  • Wide-field radiotherapy or radioisotopes such as Strontium-89 or Radium-223 ≤ 28 days prior to starting study drug (limited-field palliative radiotherapy for 1-5 fractions is permitted at anytime prior to commencement protocol therapy)
  • Brain metastases or active epidural disease (treated epidural disease is permitted)
  • Use of herbal products that may lower PSA level (e.g. saw palmetto)
  • 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.
  • Gastrointestinal disorder affecting absorption
  • Major surgery within 4 weeks of starting study treatment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

BC Cancer Agency - Abbotsford

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BC Cancer Agency - Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer Agency - Centre for the North

Prince George, British Columbia, V2N 7E9, Canada

Location

BC Cancer Agency - Fraser Valley

Surrey, British Columbia, V3V 1Z2, Canada

Location

Vancouver Prostate Centre

Vancouver, British Columbia, V5Z 1M9, Canada

Location

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BC Cancer Agency - Vancouver Island

Victoria, British Columbia, V8R 6V5, Canada

Location

Related Publications (4)

  • Annala M, Taavitsainen S, Khalaf DJ, Vandekerkhove G, Beja K, Sipola J, Warner EW, Herberts C, Wong A, Fu S, Finch DL, Oja CD, Vergidis J, Zulfiqar M, Eigl BJ, Kollmansberger CK, Nykter M, Gleave ME, Chi KN, Wyatt AW. Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition. Clin Cancer Res. 2021 Aug 15;27(16):4610-4623. doi: 10.1158/1078-0432.CCR-21-1625. Epub 2021 Jun 3.

    PMID: 34083234DERIVED

  • Jayaram A, Wingate A, Wetterskog D, Conteduca V, Khalaf D, Sharabiani MTA, Calabro F, Barwell L, Feyerabend S, Grande E, Martinez-Carrasco A, Font A, Berruti A, Sternberg CN, Jones R, Lefresne F, Lahaye M, Thomas S, Joshi S, Shen D, Ricci D, Gormley M, Merseburger AS, Tombal B, Annala M, Chi KN, De Giorgi U, Gonzalez-Billalabeitia E, Wyatt AW, Attard G. Plasma Androgen Receptor Copy Number Status at Emergence of Metastatic Castration-Resistant Prostate Cancer: A Pooled Multicohort Analysis. JCO Precis Oncol. 2019 Sep 24;3:PO.19.00123. doi: 10.1200/PO.19.00123. eCollection 2019.

    PMID: 32923850DERIVED

  • Khalaf DJ, Annala M, Taavitsainen S, Finch DL, Oja C, Vergidis J, Zulfiqar M, Sunderland K, Azad AA, Kollmannsberger CK, Eigl BJ, Noonan K, Wadhwa D, Attwell A, Keith B, Ellard SL, Le L, Gleave ME, Wyatt AW, Chi KN. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol. 2019 Dec;20(12):1730-1739. doi: 10.1016/S1470-2045(19)30688-6. Epub 2019 Nov 11.

    PMID: 31727538DERIVED

  • Khalaf DJ, Sunderland K, Eigl BJ, Kollmannsberger CK, Ivanov N, Finch DL, Oja C, Vergidis J, Zulfiqar M, Gleave ME, Chi KN. Health-related Quality of Life for Abiraterone Plus Prednisone Versus Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer: Results from a Phase II Randomized Trial. Eur Urol. 2019 Jun;75(6):940-947. doi: 10.1016/j.eururo.2018.12.015. Epub 2018 Dec 24.

    PMID: 30591354DERIVED

MeSH Terms

Interventions

Abiraterone Acetateenzalutamide

Intervention Hierarchy (Ancestors)

AndrostenesAndrostanesSteroidsFused-Ring CompoundsPolycyclic Compounds

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
OTHER
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 22, 2014

First Posted

April 29, 2014

Study Start

September 1, 2014

Primary Completion

February 4, 2020

Study Completion

February 4, 2020

Last Updated

August 7, 2020

Record last verified: 2020-08

Locations

CA(7)