Trial Overview

The DORA Trial (ClinicalTrials.gov Identifier: NCT03574571) is an open-labeled, randomized, phase III study of docetaxel versus docetaxel in combination with radium-223 (Ra-223) in subjects with metastatic castration-resistant prostate cancer (mCRPC).

Radium-223 (Ra-223), a bone-targeted alpha therapy, is a well-tolerated treatment option that prolongs survival in men with mCRPC to bone. Docetaxel targets microtubule trafficking improving survival in the mCRPC and metastatic hormone-sensitive settings.

DORA Trial principal investigator Michael Morris, MD, of the Memorial Sloan Kettering Cancer Center, New York City, NY, discusses the aims, rationale and implications of the study.

This video was recorded at the 2019 Genitourinary Cancers Symposium, held in San Francisco, CA.

Trial Design

Eligibility Screening

Patients with progressive mCRPC and >2 bone lesions

After consent is obtained and eligibility is confirmed, subjects will be registered and stratified by the following factors:

1.

Prior docetaxel for castration-sensitive disease

2.

Visceral disease
(presence or absence)

Once stratified, patients will be randomized (1:1)

Arm A*

Docetaxel 75 mg/m2 q 3 wks for 10 doses
**Prednisone twice daily

Arm B*

Docetaxel 60 mg/m2 q 3 wks for 10 doses
**Prednisone twice daily
Radium-223 55 kBq/kg q 6 wks for 6 injections

*Dexamethasone will be given per institusional practice. Growth factor support may be used per ASCO guidelines, but use as primary Prophylaxis should be avoided. Neulasta, if given, should be given 24 hours after the last study drug(s) are given.

**Docetaxel to precede Radium-223 and both treatments should be given on the same day, if feasible. If not, Radium-223 can be given the day after docetaxel.

Objectives

Primary Objective 

+-

Compare overall survival for subjects treated with docetaxel versus subjects treated with docetaxel plus radium-223.

Secondary Objectives 

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To compare:

  • Radiographic PFS as defined in PCWG3 criteria
  • Symptomatic Skeletal Event free survival
  • Time to total ALP progression
  • On-treatment alterations in QOL as assessed by FACT-P, BPI, and BFI measures between subjects who receive  docetaxel with those who receive docetaxel and radium-223

To determine if there is excessive:

  • Febrile neutropenia in subjects treated with docetaxel plus radium-223
  • Treatment discontinuation in subjects who are on their fourth line of therapy

Correlative Objectives 

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To evaluate:

  • On treatment alterations in PSA
  • Time to first SSE
  • On-treatment alterations in bone biomarkers
  • Total ALP response
  • CTC characterization at baseline and on treatment
  • CTC response
  • On-treatment AR-V7 characterization
  • On-treatment alterations in ctDNA
  • On-treatment changes in aBSI

Eligibility Criteria

Primary Inclusion Criteria 

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  • Progressive mCRPC
  • ≥ 2 bone lesions by nuclear bone scan
  • Serum testosterone < 50 ng/dL
  • ECOG ≤ 1

Primary Exclusion Criteria 

+-
  • Prior cancer directed chemo in castration resistant setting
  • > 6 prior doses of docetaxel in the castration sensitive setting.
  • ≥ 4 systemic anticancer regimens for mCRPC
  • Visceral mets with > 3 lung/liver mets or lesions > 2 cm, seen within 8 weeks prior to randomization
  • Prior systemic investigational or anti-cancer radiopharmaceutical
  • None of the following within 2 weeks or 5 half-lives, whichever is shorter, prior to randomization:
  • Investigational or other anticancer therapies
  • External beam radiotherapy
  • 5-alpha-reductase inhibitors, natural hormonally active foods, supplements known to alter PSA
  • Cord compression based on clinical findings and/or MRI
  • Known bone marrow dysplasia

Trial Locations

United States

Comprehensive Cancer Centers of Nevada
GU Research Network
Millennium Oncology
IU Simon CC
University of Michigan
Cooper MD Anderson
Midlantic Urology
University of Rochester
Roswell Park
U Mass
MSKCC
WCMC
University of North Carolina-Chapel Hill
University of Oklahoma- Stephenson Cancer Center
University of Washington (Seattle, Washington)
Helen Graham Cancer Center (Newark, Delaware)
Ochsner Medical Center (New Orleans, Louisiana)
University of Maryland (Baltimore, Maryland)
Rush University Medical Center (Chicago, Illinois)
Yale Cancer Center (New Haven, Connecticut)

The Netherlands

Erasmus MC
[Rotterdam, Netherlands]
Stichting Ziekenhuisgroep Twente (ZGT)
(Almelo, Netherlands)

Follow Us

🇳🇱 @Franciscuszorg (PI = P. Hamberg, MD) is now enrolling patients to the #DORATrial (NCT03574571), a study to test… https://t.co/J6jVkVLHnT
@DoraTrial PI @morr316 along with Dr. Larry Schwartz discuss credentialing imaging as an outcome measure in prostat… https://t.co/8jxB6ZH7Qh
RT @ThePCCTC: Happy @Movember 1st! Be part of the movement changing the face of men’s health by joining us in raising funds and awareness f…
Congratulations to @UMGCCC (PI = Arif Hussain, MD) for enrolling its first patient to the #DORATrial, an open-label… https://t.co/b3IlvKdwzi

Contact

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For additional information on the DORA Trial please visit ClinicalTrials.gov.

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