Metastatic Prostate Cancer, Pain
Conditions
Keywords
Radium-223, 14-098, Prostate Cancer Clinical Trials Consortium
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.
Interventions
DRUGRadium-223
Sponsors
University of North Carolina
New York Presbyterian Hospital
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 30% Decline in the Brief Pain Inventory (BPI) Worst Pain Item From Baseline to Week 8 | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Changes in Bone Alkaline Phosphatase (ALP) | 12 weeks | 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. |
| Number of Participants With 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Radium-223 | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Progressive Disease | 4 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Radium-223 |
|---|---|
| Age, Continuous | 69 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 29 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 29 |
| other Total, other adverse events | 22 / 29 |
| serious Total, serious adverse events | 11 / 29 |
Outcome results
Primary
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.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 | Percentage of Participants With 30% Decline in the Brief Pain Inventory (BPI) Worst Pain Item From Baseline to Week 8 | 11 Percentage of pts w/pain improvement |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radium-223 | Number of Participants With Changes in Bone Alkaline Phosphatase (ALP) | Count of non pain responders with consecutive decrease in Bone Alkaline Phosphatase | 18 Participants |
| Radium-223 | Number of Participants With Changes in Bone Alkaline Phosphatase (ALP) | Count of pain responders with consecutive decrease in Bone Alkaline Phosphatase | 9 Participants |
| Radium-223 | Number of Participants With Changes in Bone Alkaline Phosphatase (ALP) | Count of participants with no change | 2 Participants |
Secondary
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
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radium-223 | Number of Participants With Changes in Other Bone Markers: | Count of pain responder participants with consecutive decrease in N-terminal propeptide | 9 Participants |
| Radium-223 | Number of Participants With Changes in Other Bone Markers: | Count of participants with no consecutive decrease in N-terminal propeptide | 20 Participants |