Non-Randomized Trial Assessing Pain Efficacy With Radium-223 in Symptomatic Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Open, Non-Randomized Trial Assessing Pain Efficacy With Radium-223 in Symptomatic Metastatic Castration-Resistant Prostate Cancer

Conditions
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Metastatic Prostate Cancer, Pain

Intervention / Treatment
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* Drug: Radium-223


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radium-223<br>Radium Ra 223 dichloride will be administered as a bolus intravenous (IV) injection (up to 1 minute) at intervals of every 4 weeks for up to 6 cycles. The dosage of Radium Ra 223 dichloride after implementation of the new 2015 NIST standard is 55kBq/kg body weight. | Drug: Radium-223<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 30% Decline in the Brief Pain Inventory (BPI) Worst Pain Item From Baseline to Week 8 | Defined as a 30% decline in the Brief Pain Inventory/BPI worse pain item from baseline to week 8, with a confirmed reduction at week 12 without an escalation of the subject's pain regimen from Step 1 to Step 2 or Step 2 to Step 3 of the WHO analgesic ladder.) The baseline BPI worst pain score average will be based on the worst pain scores completed by the participant in the 7 consecutive pretreatment days. A minimum of 4 days of pain scores must be completed by the participant in the 7 day window in order to calculate the average worst pain score. The BPI scale defines pain as follows: Worst Pain Score: 1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Changes in Bone Alkaline Phosphatase (ALP) | Number of participants with changes from baseline to 12 weeks (or earlier for those who discontinue study therapy). Maximum change (rise or fall) in bone Alkaline phosphatase (ALP) during the treatment period reported. | 12 weeks | 
| Number of Participants With Changes in Other Bone Markers: | Serum C-telopeptide (sCTX-1) N-terminal propeptide of procollagen type 1 (PINP) Changes in total-ALP will be defined as for bone-ALP above | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radium-223, 14-098, Prostate Cancer Clinical Trials Consortium