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

NCT ID: NCT02346526

Last Updated: 2022-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Prostate Cancer; Castration-resistant Prostate Cancer; Castration-resistant Prostate Cancer Metastatic to Bone

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radium-223 dichloride

After the screening procedures confirm that a patient is eligible to participate in the research study.

Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring.

• Blood Tests
• CT scan
• Bone scan
• FACBC PET/MRI in a subset of participants

Group Type: EXPERIMENTAL

Blood Tests

Intervention Type: PROCEDURE

Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93.

CT scan

Intervention Type: PROCEDURE

Standard CT scans will be carried out prior to treatment, week 9, and week 25.

FACBC PET/MRI in a subset of participants

Intervention Type: PROCEDURE

Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9.

Radium-223 dichloride

Intervention Type: DRUG

Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments.

bone scan

Intervention Type: PROCEDURE

Standard bone scans will be carried out prior to treatment, week 9, and week 25.

Interventions

Blood Tests

Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93.

Intervention Type: PROCEDURE

CT scan

Standard CT scans will be carried out prior to treatment, week 9, and week 25.

Intervention Type: PROCEDURE

FACBC PET/MRI in a subset of participants

Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9.

Intervention Type: PROCEDURE

Radium-223 dichloride

Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments.

Intervention Type: DRUG

bone scan

Standard bone scans will be carried out prior to treatment, week 9, and week 25.

Intervention Type: PROCEDURE

Other Intervention Names

Xofigo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Philip J. Saylor, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philip J Saylor, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

ONC-2013-119

Identifier Type: OTHER

Identifier Source: secondary_id

14-375

Identifier Type: -

Identifier Source: org_study_id