Clinical trial NCT03574571: A Study to Test Radium-223 With Docetaxel in Patients With Prostate Cancer
Official title: Phase III Trial of Docetaxel vs. Docetaxel and Radium-223 for Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Radium-223
Docetaxel
18-150
C16-174
DORA Trial
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2018-07-02
Enrollment: 738
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an open-labeled, randomized, phase III study of docetaxel versus docetaxel in combination with radium-223 in subjects with mCRPC.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare any good and bad effects of using radium-223 along with docetaxel chemotherapy treatment versus using docetaxel alone. Earlier studies helped show that the combination is safe, but the combination has not been proven to work better than either drug alone. The goal of this study is to find out if combining docetaxel and radium-223 is better than giving either drug by itself.


Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent (ICF) and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.

NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.

* Males 18 years of age and above
* Histological or cytological proof of prostate cancer
* Documented progressive mCRPC based on at least one of the following criteria:

  1. PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 1.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 1.0 ng/mL.
  2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the LD of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions.
  3. Progression of bone disease (evaluable disease) or two or more new bone lesions by bone scan.
* Two or more bone lesions
* ECOG 0- 1
* Normal organ function with acceptable initial laboratory values within 14 days of randomization:

  * Albumin \> 30 g/L
  * ANC ≥ 1.5 x 10\^9/L
  * Hemoglobin ≥ 10 g/dL
  * Platelet count ≥ 100 x 10\^9/L
  * Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN)
  * Bilirubin ≤ ULN (unless documented Gilbert's disease)
  * SGOT (AST) ≤ 1.5 x ULN
  * SGPT (ALT) ≤ 1.5 x ULN
  * WBC count ≥ 3 x 10\^9/L
* Subjects must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 30 days after the last dose of study drug. Sperm donation is prohibited during the study and for 30 days after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
* Serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomy.
* All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less.
* Willing and able to comply with the protocol, including follow-up visits and examinations

Exclusion Criteria:

* Received any other investigational therapeutic agents or other anticancer therapies within 4 weeks prior to randomization.

  °Note: If this requirement to have a washout of 2 weeks or 5 half-lives prior to randomization causes potential treatment delay due to Radium-223 importation timelines, the PCCTC must be contacted at pcctc@mskcc.org to request approval to randomize the subject prior to the completion of the washout. Requests for early randomization must be accompanied by written assurance by the site that the washout will be completed prior to treatment start.
* Received external beam radiotherapy within the 4 weeks prior to randomization.

  ° Note: If prolonging randomization to complete EBRT washout causes potential treatment delay due to Radium-223 importation timelines, the PCCTC must be contacted at pcctc@mskcc.org to request approval to randomize the subject prior to the completion of the washout. Requests for early randomization must be accompanied by written assurance by the site that the washout will be completed prior to treatment start.
* Has an immediate need for external beam radiotherapy.
* Has received any systemic bone-seeking radiopharmaceutical in the past.
* Has received any prostate cancer directed chemotherapy in the castration resistant setting. Subjects who have received up to 6 prior doses of docetaxel in the castration sensitive setting are permitted if they have not experienced disease progression within 36 weeks of last treatment with docetaxel.
* Has received four or more systemic anticancer regimens for mCRPC.

  * Treatment with docetaxel or abiraterone for non-castrate metastatic disease is permissible and does not count towards the lines of therapy for mCRPC
  * A 'line' is a regimen. Combinations of hormones and other types of therapies count as single lines.
* Has known Grade ≥3 docetaxel-related toxicities or docetaxel toxicity related dose interruption or discontinuation.
* Has received blood transfusions or growth factors within the last 4 weeks prior to randomization.
* Symptomatic nodal disease (i.e., scrotal, penile, or leg edema).
* Has visceral metastases with ≥ 3 lung and/or liver metastases or individual lesion ≥2 cm, as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to randomization.
* Symptomatic loco-regional disease that causes ongoing Grade 3 or Grade 4 urinary or rectal symptoms.
* Subjects with a "currently active" second malignancy other than non-melanoma skin cancers or non-invasive bladder cancers or other in-situ or non-invasive malignancies. Subjects are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
* Has imminent or established cord compression based on clinical findings and/or MRI.
* Known bone marrow dysplasia
* Has received any of the following in the 4 weeks prior to randomization: 5-alpha-reductase inhibitors, herbal medications, natural hormonally active foods (e.g., phytoestrogens) or other food supplements known to alter PSA in humans
* Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including but not limited to:

  * Uncontrolled infection
  * NYHA III or IV heart failure
  * Crohn's disease or those with ulcerative colitis who have not undergone a colectomy
  * Known active infection with HIV, Hepatitis B or Hepatitis C

Primary outcomes:
measure: Overall survival
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: New Haven
country: United States
facility: Yale University- Yale Cancer Center
state: Connecticut
city: Newark
country: United States
facility: Helen Graham Cancer Center (Christiana Care)
state: Delaware
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Miami
country: United States
facility: Mount Sinai Medical Center (Miami)
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: XCancer Omaha / Urology Cancer Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Saddle Brook
country: United States
facility: New Jersey Urology
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Oncology and Hematology
state: New Mexico
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital-Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Bronx VA Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Monroe
country: United States
facility: Atrium Health/ Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Kettering
country: United States
facility: Dayton Physicians Network
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Houston
country: United States
facility: Millennium Physicians
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Barretos
country: Brazil
facility: Hospital de Amor de Barretos (Fundação Pio XII) / Barretos Cancer Hospital
state: Dr. Paulo Prata
city: Boa Vista
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira (IMIP)
state: Pernambuco
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Câncer/IBCC
state: State Of São Paulo
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Porto Alegre
country: Brazil
facility: CPORS - Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento (HMV)
city: São Paulo
country: Brazil
facility: Beneficência Portuguesa
city: São Paulo
country: Brazil
facility: Centro de Pesquisas São Lucas - Sociedade Campineira de Educação e Instrução (SCEI)
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
state: Plesmanlaan
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgrouep Alkmaar (NWZ)
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente (ZGT)
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Center
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Hilversum
country: Netherlands
facility: Tergooi Hospital
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis (CWZ)
city: Rotterdam
country: Netherlands
facility: Erasmus MC Cancer Institute
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Utrecht
country: Netherlands
facility: St. Antonius Ziekenhuis (Utrecht)
city: Zwolle
country: Netherlands
facility: Isala Kliniek
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias (HUCA)
state: Avenida De Roma S/n
city: Madrid
country: Spain
facility: Ramón y Cajal Hospital
state: Community Of Madrid
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Barcelona
country: Spain
facility: Clinic de Barcelona
city: Castelló de la Plana
country: Spain
facility: Hospital Provincial de Castellón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocío
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Michael Morris, MD
role: PRINCIPAL_INVESTIGATOR
References: