non-randomized trial assessing pain efficacy with radium-223 in symptomatic metastatic castration-resistant prostate cancer

Conditions: Metastatic Prostate Cancer; Pain

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.

Keywords: radium-223 14-098 prostate cancer clinical trials consortium