Clinical Trials /

Investigation of Radium-223 Dichloride (Xofigo), a Treatment That Gives Off Radiation That Helps Kill Cancer Cells, Compared to a Treatment That Inactivates Hormones (New Antihormonal Therapy, NAH) in Patients With Prostate Cancer That Has Spread to the Bone Getting Worse on or After Earlier NAH

NCT04597125

Description:

Researchers in this study want to compare how well drug radium-223 dichloride (Xofigo) and new (novel) anti-hormonal (NAH) therapy work in participants with prostate gland cancer which has spread to the bone and progressed on or after one line of NAH therapy. Meanwhile researchers want to compare the safety of radium-223 dichloride and NAH therapy. Radium-223 dichloride is known as a radioactive drug that is taken up by bones after it is injected into the body. It works by giving off a type of radioactivity that travels a very short distance and kills the tumor cells that have spread to the bone without major effects to the healthy cells. It has been approved in many countries for the treatment of patients with prostate cancer which has spread to the bone. The NAH drugs used in this study will be either abiraterone acetate (Zytiga) (plus prednisone/prednisolone) or enzalutamide (Xtandi). Both of them are standard approved medications which are used in the treatment of advanced prostate cancer. Participants in this study will receive either Radium-223 dichloride or a NAH therapy. Radium-223 dichloride will be given as an infusion into one of the veins on Day 1 of each 4-week cycle for a total of up to 6 cycles. Oral NAH therapy will be given per the standard approved dose once daily until the disease has progressed. Participants will visit the hospital or clinic every 2 weeks for the first 6 cycles, and only on the first day of each cycle from cycle 7 and onwards. Observation for each participant will last for about 2 years in total. Blood and urine samples will be collected from the participants and participants will be asked to complete questionnaires about the well-being and the pain.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: Study to Learn More About a Drug Called Radium-223 Dichloride (Xofigo) Given and Compared With the Standard Dose of a New (Novel) Anti-hormonal Therapy (NAH) in Adult Male Participants With Prostate Gland Cancer Which Spread to the Bone
  • Official Title: A Phase 4, Randomized, Open-label, Multicenter Efficacy and Safety Study of Standard Dose of Radium-223 Dichloride vs. Standard Doses of Novel Anti-hormonal Therapy (NAH) in Patients With Bone Dominant Metastatic Castration Resistant Prostate Cancer (mCRPC) Progressing on/After One Line of NAH

Clinical Trial IDs

  • ORG STUDY ID: 20510
  • SECONDARY ID: 2019-000476-42
  • NCT ID: NCT04597125

Conditions

  • Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Interventions

DrugSynonymsArms
Radium-223 dichloride (Xofigo, BAY88-8223)Arm A
NAH therapySecond novel anti-hormonal therapyArm B

Purpose

Researchers in this study want to compare how well drug radium-223 dichloride (Xofigo) and new (novel) anti-hormonal (NAH) therapy work in participants with prostate gland cancer which has spread to the bone and progressed on or after one line of NAH therapy. Meanwhile researchers want to compare the safety of radium-223 dichloride and NAH therapy. Radium-223 dichloride is known as a radioactive drug that is taken up by bones after it is injected into the body. It works by giving off a type of radioactivity that travels a very short distance and kills the tumor cells that have spread to the bone without major effects to the healthy cells. It has been approved in many countries for the treatment of patients with prostate cancer which has spread to the bone. The NAH drugs used in this study will be either abiraterone acetate (Zytiga) (plus prednisone/prednisolone) or enzalutamide (Xtandi). Both of them are standard approved medications which are used in the treatment of advanced prostate cancer. Participants in this study will receive either Radium-223 dichloride or a NAH therapy. Radium-223 dichloride will be given as an infusion into one of the veins on Day 1 of each 4-week cycle for a total of up to 6 cycles. Oral NAH therapy will be given per the standard approved dose once daily until the disease has progressed. Participants will visit the hospital or clinic every 2 weeks for the first 6 cycles, and only on the first day of each cycle from cycle 7 and onwards. Observation for each participant will last for about 2 years in total. Blood and urine samples will be collected from the participants and participants will be asked to complete questionnaires about the well-being and the pain.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalParticipants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of NAH will be randomized to receive radium-223 dichloride
  • Radium-223 dichloride (Xofigo, BAY88-8223)
Arm BActive ComparatorParticipants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of NAH will be randomized to receive second novel anti-hormonal therapy (NAH)
  • NAH therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Participants who have histologically confirmed adenocarcinoma of the prostate.

          -  Participants with metastatic castrate resistant prostate cancer (mCRPC) progressing
             on/after one line of novel anti-hormonal therapy (NAH) (after being treated for at
             least 3 months) for metastatic prostate cancer (mHSPC and mCRPC).

          -  One prior taxane treatment regimen (at least 2 cycles) for metastatic prostate cancer
             (mHSPC and mCRPC) or refusal or ineligibility of such a regimen.

          -  Prostate cancer progression documented by PSA according to the Prostate Cancer Working
             Group 3 (PCWG3) criteria or radiological progression according to RECIST, version 1.1.

          -  At least 2 bone metastases on bone scan within 4 weeks prior to randomization with no
             current or history of lung, liver, other visceral, and / or brain metastasis.

          -  Symptomatic prostate cancer. A worst pain score (WPS) of at least 1 on the Brief Pain
             Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours). This is to be
             assessed once during the Screening period.

          -  Maintenance of medical castration or surgical castration with testosterone less than
             50 ng/dL (1.7 nmol/L). If the participant is being treated with luteinizing hormone
             releasing hormone (LHRH) agonists or antagonists (participant who has not undergone
             orchiectomy), this therapy must have been initiated at least 4 weeks prior to
             randomization and must be continued throughout the study.

          -  Participants must be on a BHA treatment, such as bisphosphonates or denosumab
             treatment unless such treatment is contraindicated or not recommended per
             investigator's judgement and inclusion is agreed to by the medical monitor.

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.

          -  Life expectancy ≥ 6 months.

          -  Able to swallow abiraterone and prednisone/prednisolone or enzalutamide as whole
             tablets/capsules.

          -  Laboratory requirements:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

               -  Platelet count ≥ 100 x 10^9/L

               -  Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L; 5.6 mmol/L)

               -  Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (except
                  for participants with documented Gilbert's disease)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

               -  Creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR) ≥ 30
                  mL/min/1.73 m^2 as calculated using the Cockcroft-Gault equation

               -  International normalized ratio (INR) of prothrombin time (PT; PT-INR) and partial
                  thromboplastin time (PTT) ≤ 1.5 times the ULN. Participants treated with warfarin
                  or heparin will be allowed to participate in the study if no underlying
                  abnormality in coagulation parameters exists per prior history; weekly evaluation
                  of PT-INR / PTT will be required until stability is achieved (as defined by local
                  standard of care and based on pre-study PT-INR / PTT values)

               -  Serum albumin > 30 g/L

               -  Serum potassium ≥ 3.5 mmol/L

          -  Capable of giving signed informed consent

        Exclusion Criteria:

          -  Active infection or other medical condition that would make prednisone / prednisolone
             (corticosteroid) use contraindicated.

          -  Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg
             prednisone / prednisolone twice daily.

          -  Pathological finding consistent with tumors with neuroendocrine features or small cell
             carcinoma of the prostate.

          -  History of osteoporotic fracture

          -  History of visceral metastasis, or presence of visceral metastasis detected by
             screening imaging examinations.

          -  History of or known brain metastasis.

          -  Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.

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

          -  Imminent spinal cord compression based on clinical findings and / or magnetic
             resonance imaging (MRI). Participants with history of spinal cord compression should
             have completely recovered.

          -  Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood
             pressure ≥ 95 mmHg). Participants with a history of hypertension are allowed provided
             blood pressure is controlled by anti-hypertensive treatment.

          -  Active or symptomatic viral hepatitis

          -  History of pituitary or adrenal dysfunction

          -  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 5.0 Grade 2

               -  Clinically significant heart disease as evidenced by myocardial infarction, or
                  arterial thrombotic events in the past 6 months, severe or unstable angina, or
                  New York Heart Association (NYHA) Class II to IV heart disease or cardiac
                  ejection fraction measurement of <50% at baseline

               -  Atrial fibrillation, or other cardiac arrhythmia requiring therapy

               -  Crohn's disease or ulcerative colitis

               -  Bone marrow dysplasia

               -  Moderate and severe hepatic impairment (Child-Pugh Classes B and C)

               -  Unmanageable fecal incontinence.

          -  Any condition, which in the opinion of the investigator would preclude participation
             in this trial (eg, history of seizure).

          -  Hypersensitivity to the active substances or to any excipients of radium-223
             dichloride, or abiraterone acetate or enzalutamide.

          -  Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, rhenium-188,
             or radium-223.

          -  Prior hemibody external radiotherapy is excluded. Participants who received other
             types of prior external radiotherapy are allowed provided that the bone marrow
             function is assessed and meets the protocol requirements for Hb, ANC, and platelet
             count.

          -  Blood transfusion or erythropoietin stimulating agents 4 weeks prior to Screening and
             during the whole Screening period before randomization.

          -  Excessive intake of biotin above the recommended daily dose of 30 μg. Biotin is found
             in multivitamins, including prenatal multivitamins, biotin supplements, and dietary
             supplements for hair, skin, and nail growth at levels that may interfere with
             laboratory tests.

          -  Prior administration of an investigational therapeutic for CRPC.

          -  Previous (within the last 4 weeks of randomization) or concurrent participation in any
             interventional clinical study with investigational study drug administration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to five years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time to first symptomatic skeletal event (SSE)
Time Frame:Up to five years
Safety Issue:
Description:
Measure:Radiological Progression-free survival (rPFS)
Time Frame:Up to five years
Safety Issue:
Description:rPFS is defined as the time from the date of randomization to the date of confirmed radiological progression or death, whichever occurs first.
Measure:Time to pain progression (BPI-SF)
Time Frame:Up to five years
Safety Issue:
Description:The Brief Pain Inventory-Short Form (BPI-SF) is a self-administered questionnaire with 11 items designed to evaluate the intensity of, and the impairment caused by pain. Four items measure pain intensity using 0 ("no pain") to 10 ("pain as bad as you can imagine") numeric rating scales, and 7 items measure the level of interference with function caused by pain using 0 (no interference) to 10 (complete interference) rating scales.
Measure:Adverse events assessments using NCI CTCAE (v5.0)
Time Frame:After first administration of study intervention up to 30 days after the last dose of study intervention
Safety Issue:
Description:
Measure:Incidence of fractures
Time Frame:Up to five years
Safety Issue:
Description:
Measure:Time to deterioration of FACT-P total score
Time Frame:Up to five years
Safety Issue:
Description:The FACT-P questionnaire assesses prostate cancer-related quality of life. The FACT-P total score is the sum of the scores of 39 items of the questionnaire and ranges from 1 to 156, the higher the score, the better the quality of life of prostate cancer patients.

Details

Phase:Phase 4
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Last Updated

October 22, 2020