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

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

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

PCWG3 Overview

Dora PI Dr. Michael Morris and Dr. Lawrence Schwartz describe PCWG3 Criteria

Eligibility Criteria

Primary Inclusion Criteria

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