Clinical trial NCT02278055: Non-Randomized Trial Assessing Pain Efficacy With Radium-223 in Symptomatic Metastatic Castration-Resistant Prostate Cancer
Official title: Phase II Open, Non-Randomized Trial Assessing Pain Efficacy With Radium-223 in Symptomatic Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Pain
Keywords: Radium-223
14-098
Prostate Cancer Clinical Trials Consortium
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: New York Presbyterian Hospital
First posted: 2014-10-29
Enrollment: 29
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.


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.

Primary outcomes:
measure: Percentage of Participants With 30% Decline in the Brief Pain Inventory (BPI) Worst Pain Item From Baseline to Week 8
timeFrame: 8 weeks
Secondary outcomes:
measure: Number of Participants With Changes in Bone Alkaline Phosphatase (ALP)
timeFrame: 12 weeks
measure: Number of Participants With Changes in Other Bone Markers:
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital-Weill Medical College of Cornell University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Michael Morris, MD
role: PRINCIPAL_INVESTIGATOR
References: