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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT02278055

Collaborator

University of North Carolina (Other), New York-Presbyterian Hospital Cornell Medical Center (Other)

Enrollment

Locations

Arm

87.9

Actual Duration (Months)

9.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Prostate Cancer Pain	Drug: Radium-223	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Oct 8, 2014

Actual Primary Completion Date :

Feb 2, 2022

Actual Study Completion Date :

Feb 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radium-223 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

Arm

Intervention/Treatment

Experimental: Radium-223

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

Outcome Measures

Primary Outcome Measures

pain response [8 weeks]
(defined as a 30% decline in the BPI worse pain item from baseline to week 8, with a confirmed reduction at week 12 without an escalation of the subjects pain regimen from Step 1 to Step 2 or Step 2 to Step 3 of the WHO analgesic ladder.)

Secondary Outcome Measures

Changes in Bone Alkaline phosphatase (ALP) [12 weeks]
Percentage of change 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 for each patient as a waterfall plot
Changes in other bone markers: [1 year]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
2	New York Presbyterian Hospital-Weill Medical College of Cornell University	New York	New York	United States	10065
3	University of North Carolina	Chapel Hill	North Carolina	United States	27514