A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer
Condition: Prostate Cancer; Castration-resistant Prostate Cancer; Castration-resistant Prostate Cancer Metastatic to Bone
MeSH terms: Prostatic Neoplasms
Intervention: Blood Tests; CT scan; FACBC PET/MRI in a subset of participants; Radium-223 dichloride; bone scan
Intervention description: Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93.; Standard CT scans will be carried out prior to treatment, week 9, and week 25.; Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9.; Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments.; Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Intervention MeSH terms: Radium Ra 223 dichloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Castration-resistant prostate cancer; Castration-resistant prostate cancer metastatic to bone

Summary:

      The purpose of this study is to look for markers of how Ra-223 improves the lives of men with
      prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds
      non-standard testing in an attempt to gain insight about how the drug works and how best to
      track patients who are receiving the drug.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male age ≥ 18 years.

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate. Life
             expectancy of at least 6 months.

          -  ECOG performance status of zero, one, or two.

          -  Bone-predominant metastatic CRPC: at least two skeletal metastases on bone scan with
             no lung, liver, and/or brain metastasis (lymph node metastasis is allowed).

          -  Symptomatic as defined by either of the following:

               -  (a) Regular use of analgesic medication for cancer-related bone pain (≥ level 1;
                  WHO ladder for cancer pain), or

               -  (b) Treatment with EBRT for bone pain (though EBRT must be completed ≥12 weeks
                  prior to enrollment in this trial).

          -  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 NCI-CTCAE v4.0 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.

          -  Acceptable hematology and serum biochemistry screening values:

               -  White Blood Cell Count (WBC) ≥ 3,000/mm3

               -  Absolute Neutrophil Count (ANC) ≥ 1,500/mm3

               -  Platelet (PLT) count ≥ 100,000/mm3

               -  Hemoglobin (HGB) ≥10 g/dl (Please note: it is acceptable from the standpoint of
                  study eligibility to undergo transfusion in order to achieve hemoglobin ≥ 10
                  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 ≤ 1.5 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 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.