A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer

A Single-arm Open Label Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer

The purpose of this study is to look for markers of how Ra-223 improves the lives of men with prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

This research study is designed to examine a treatment strategy that is standard but still relatively new. Ra-223 consists of a series of six infusions given once every 4 weeks. It was FDA approved in 2013 for the treatment of prostate cancer that has spread to bone and has grown despite ADT ("hormonal therapy").

Ra-223 was approved because it was shown to improve the length of the lives of the men with prostate cancer who received it. Despite that important benefit, it is not known to improve other standard markers of prostate cancer such as PSA blood tests (a blood marker that is used to track cancer activity in men who have prostate cancer) and standard imaging scans such as bone scans and computed tomography (CT) scans. If participants and their doctors do not have good markers of whether or not the cancer is responding to therapy, it is harder to make decisions about whether to continue that therapy. This is a current problem.

This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.

Inclusion Criteria:

• Male age ≥ 18 years.

• Histologically or cytologically confirmed adenocarcinoma of the prostate. Life expectancy of at least 6 months.

• ECOG performance status of zero, one, or two.

• Bone-predominant metastatic CRPC: at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed).

• Symptomatic as defined by either of the following:

  • (a) Regular use of analgesic medication for cancer-related bone pain (≥ level 1; WHO ladder for cancer pain), or
  • (b) Treatment with EBRT for bone pain (though EBRT must be completed ≥12 weeks prior to enrollment in this trial).

• Judged by investigator to have progressive disease sufficient to clinically justify standard-of-care radium-223 treatment.

• Subjects must be able to understand and be willing to sign the written informed consent form.

• All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).

• No intention to use cytotoxic chemotherapy within the next 6 months. Subjects must agree to use adequate contraception beginning at the signing of the ICF until at least 6 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator.

• Acceptable hematology and serum biochemistry screening values:

  • White Blood Cell Count (WBC) ≥ 3,000/mm3
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
  • Platelet (PLT) count ≥ 100,000/mm3
  • Hemoglobin (HGB) ≥10 g/dl (Please note: it is acceptable from the standpoint of study eligibility to undergo transfusion in order to achieve hemoglobin ≥ 10 g/dl)
  • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 x ULN
  • Albumin > 25 g/L

• Willing and able to comply with the protocol, including follow-up visits and examinations.

Exclusion Criteria:

• Treatment with cytotoxic chemotherapy within previous 28 days, or failure to recover from AEs due to cytotoxic chemotherapy administered more than 28 days previous (however, ongoing neuropathy is permitted).

• Received any investigational compound within 28 days prior to the first dose of study drug or planned during the treatment period or follow-up.

• Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases.

• Received previous radiotherapy to approximately >25% of bone marrow.

• Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer).

• Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality.

• Presence of brain metastases.

• Lymphadenopathy exceeding 6 cm in short-axis diameter.

• Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.

• Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.

• 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
  • Known bone marrow dysplasia

• Fecal incontinence.

• Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.