Non-Randomized Trial Assessing Pain Efficacy With Radium-223 in Symptomatic Metastatic Castration-Resistant Prostate Cancer
Condition: Metastatic Prostate Cancer; Pain
MeSH terms: Prostatic Neoplasms
Intervention: Radium-223
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radium-223; 14-098; Prostate Cancer Clinical Trials Consortium

Summary:

      The purpose of this study is to find out if Radium-223 is effective in reducing cancer pain
      within 12 weeks of treatment. In order to see if Radium-223 is effective, the patient's level
      of pain will be followed throughout the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males aged 18 years of age and above

          -  Histological or cytological proof of prostate adenocarcinoma

          -  Castrate serum testosterone level: ≤50 ng/dL (≤1.7 nmol/L)

          -  Patients who have experienced disease progression despite initial hormonal therapy,
             either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen,
             must first progress through anti- androgen withdrawal prior to being eligible. The
             minimum time frame to document failure of anti-androgen withdrawal will be four weeks.
             Patients on second-line (or beyond) hormonal maneuvers, and patients who had no PSA
             decline on combined androgen blockade as first line therapy, need not progress through
             AAW in order to be eligible.

          -  Known progressive castration-resistant disease, defined as:

               -  Serum PSA progression defined as two consecutive increases in PSA over a previous
                  reference value within 6 months of first treatment, each measurement at least one
                  week apart. Serum PSA at screening ≥ 2 ng/mL or

               -  Documented appearance of new lesions by bone scintigraphy

          -  ECOG Performance Status of 0-2 2 or more bone metastases demonstrated on bone
             scintigraphy

          -  Pain at baseline as measured by a BPI worst pain score average of ≥ 3. The BPI worst
             pain score average will be based on the worst pain scores completed by the patient in
             the 7 consecutive pretreatment days. A minimum of 4 days of pain scores must be
             completed by the patient in the 7 day window in order to calculate the average worst
             pain score. The investigator will optimize the subject's pain regimen prior to study
             entry.

          -  Normal organ function with acceptable initial laboratory values:

               -  WBC ≥ 3 x 109 /L

               -  ANC ≥ 1.5 x 109 /L

               -  Platelets ≥ 100 x 109 /L

               -  Hemoglobin ≥ 9.0 g/dL

               -  Creatinine < 1.5 x institutional upper limit of normal (ULN)

               -  Bilirubin ≤ 1.5 x ULN

               -  AST/ALT ≤ 2.5 x ULN

               -  Albumin > 25 g/L

          -  All acute toxicities as a result of any prior treatment must have resolved to
             NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF)
             [Note: Ongoing grade 2 neuropathy as a result of treatment with a cytotoxic
             chemotherapy regimen is permitted]

          -  Life expectancy of at least 6 months

          -  Willing and able to provide written informed consent and HIPAA authorization for the
             release of personal health information NOTE: HIPAA authorization may be either
             included in the informed consent or obtained separately

          -  Willing and able to comply with the protocol, including follow-up visits, examinations
             as well as having the ability to self-report pain and fatigue using a Patient Reported
             Outcome (PRO) instrument

          -  Willingness to use adequate methods of contraception beginning at the signing of the
             ICF until at least 30 days after the last dose of study drug

        Exclusion Criteria:

          -  Prior exposure to Radium-223

          -  Received an investigational therapy within the 4 weeks prior to registration or is
             scheduled to receive one during the treatment period

          -  Received a new anti-cancer agent within 4 weeks prior to registration

          -  Received external beam radiotherapy within 4 weeks prior registration

          -  Received systemic therapy with radionuclides (e.g. strontium-89, samarium-153,
             rhenium-186 or rhenium-188) for the treatment of bone metastases

          -  Treatment with cytotoxic chemotherapy within 4 weeks prior to registration

          -  Symptomatic nodal disease, i.e. scrotal, penile or leg edema. Visceral metastases
             (including cerebral metastases) from CRPC (>2 lung and/or liver metastases [size
             ≥2cm]; Lymphadenopathy exceeding 6 cm in short-axis diameter or any size pelvic
             lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis), as
             assessed by CT, MRI or chest X-ray within the 8 weeks prior registration.

          -  Concurrent chemotherapy. Patients may be on other non-chemotherapy anti-cancer
             treatments, per FDA labeling of Radium-223, provided that these are not changed during
             the primary pain assessment period Major surgery within 30 days prior to registration.

          -  Imminent spinal cord compression based on clinical findings and/or magnetic resonance
             imaging (MRI). Treatment should be completed for spinal cord compression.

          -  Patients 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.
             Patients who have completed therapy for a prior malignancy and are free of disease for
             ≥3 years are eligible.

          -  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

               -  Bone marrow dysplasia

               -  Fecal incontinence

          -  Any other condition which, in the opinion of the Investigator, would make the subject
             unsuitable for trial participation

          -  NOTE: Any patient found to be ineligible prior to treatment initiation will require
             re-screening.