Radium Ra 223 Dichloride in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Status: Active

Description

This phase II trial studies how well radium Ra 223 dichloride works in treating patients with prostate cancer that has spread to the bone (metastatic) and is resistant to hormone therapy. Radium Ra 223 dichloride is a radioactive drug that may kill tumor cells by damaging the tumor cells deoxyribonucleic acid (DNA) with limited toxicity to nearby healthy bone tissue. Studying samples of blood in the laboratory from patients receiving radium Ra 223 dichloride may help doctors identify and learn more about biomarkers related to cancer. It may also help doctors understand how well patients respond to treatment.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • Life expectancy of at least 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of zero, one, or two
  • Bone-predominant metastatic castration resistant prostate cancer (CRPC): at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed)
  • Judged by investigator to have progressive disease sufficient to clinically justify standard-of-care radium-223 treatment
  • Subjects must be able to understand and be willing to sign the written informed consent form
  • All acute toxic effects of any prior treatment have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.0 grade 1 or less at the time of signing the informed consent form (ICF)
  • No intention to use cytotoxic chemotherapy within the next 6 months
  • Subjects must agree to use adequate contraception beginning at the signing of the ICF until at least 6 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator
  • White blood cell count (WBC) >= 3,000/mm^3
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet (PLT) count >= 100,000/mm^3
  • Hemoglobin (HGB) >= 9 g/dl (please note: it is acceptable from the standpoint of study eligibility to undergo transfusion in order to achieve hemoglobin >= 9 g/dl)
  • Total bilirubin level =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine =< 2 x ULN
  • Albumin > 25 g/L
  • Willing and able to comply with the protocol, including follow-up visits and examinations

Exclusion Criteria

  • Treatment with cytotoxic chemotherapy within previous 28 days, or failure to recover from adverse events (AEs) due to cytotoxic chemotherapy administered more than 28 days previous (however, ongoing neuropathy is permitted)
  • Received any investigational compound within 28 days prior to the first dose of study drug or planned during the treatment period or follow-up
  • Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony metastases
  • Received previous radiotherapy to approximately > 25% of bone marrow
  • Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
  • Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality
  • Presence of brain metastases
  • Lymphadenopathy exceeding 6 cm in short-axis diameter
  • Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis
  • Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI); treatment should be completed for spinal cord compression
  • Any other serious illness or medical condition, such as but not limited to: * Any infection >= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 grade 2 * Cardiac failure New York Heart Association (NYHA) III or IV * Crohn’s disease or ulcerative colitis * Known bone marrow dysplasia
  • Fecal incontinence
  • Any condition which, in the investigator’s opinion, makes the subject unsuitable for trial participation

Locations & Contacts

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Philip James Saylor
Phone: 617-724-4000
Email: psaylor@partners.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the quantitative effect of Ra-223 (radium Ra 223 dichloride) on 99mTc-MDP (technetium Tc-99m medronate) bone scan in men with castration-resistant prostate cancer metastatic to bone.

SECONDARY OBJECTIVES:

I. Description of mean percent change in bone scan lesion area by 18-month survival status.

II. The evaluation of the effects of Ra-223 by the following measures: A) imaging biomarkers: concurrent conventional assessments including computed tomography scans and baseline assessments including fluciclovine position emission tomography (PET) (if assigned to PET), 99mTc MDP bone scan, and blood testing; B) standard and novel circulating tumor cell assays: circulating tumor cell (CTC) number by Food and Drug Administration (FDA)-approved assay (Verides CellSearch) and CTC translational biomarkers by microfluidic platform (e.g. enumeration, androgen receptor signaling, proliferative index by Ki67 staining); C) circulating biomarkers of the tumor microenvironment: bone turnover markers (serum bone specific alkaline phosphatase, N-telopeptide) and plasma biomarkers of inflammation and angiogenesis; D) patient reported pain and quality of life: determine rate of confirmed pain response at week 12 of study treatment and evaluate change in patient reported quality of life as measured by validated assessment tools.

OUTLINE:

Patients receive radium Ra 223 dichloride intravenously (IV) over 1 minute on day 1. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up at 1, 4, and 18 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Philip James Saylor

Trial IDs

Primary ID 14-375
Secondary IDs NCI-2015-00625, ONC-2013-119
Clinicaltrials.gov ID NCT02346526