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

• ClinicalTrials.gov Identifier: NCT04597125
• Recruitment Status: Recruiting
• First Posted: October 22, 2020
• Last Update Posted: March 23, 2021
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: October 16, 2020
• First Posted Date: October 22, 2020
• Last Update Posted Date: March 23, 2021
• Actual Study Start Date: November 9, 2020
• Estimated Primary Completion Date: April 25, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 16, 2020): Overall survival (OS) [ Time Frame: Up to five years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 16, 2020)

• Time to first symptomatic skeletal event (SSE) [ Time Frame: Up to five years ]
• Radiological Progression-free survival (rPFS) [ Time Frame: Up to five years ]
  rPFS is defined as the time from the date of randomization to the date of confirmed radiological progression or death, whichever occurs first.
• Time to pain progression (BPI-SF) [ Time Frame: Up to five years ]
  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.
• 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 ]
• Incidence of fractures [ Time Frame: Up to five years ]
• Time to deterioration of FACT-P total score [ Time Frame: Up to five years ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Intervention

• Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
  Participants will receive Radium-223 (BAY88-8223) every 4 weeks for a total of 6 administrations via intravenous (IV) injection
• Drug: NAH therapy
  Participants will receive continuous NAH (either Abiraterone acetate plus prednisone/prednisolone [AAP] or enzalutamide) by mouth (per os) daily
  Other Name: Second novel anti-hormonal therapy

Study Arms

• Experimental: Arm A
  Participants with bone dominant metastatic castration resistant prostate cancer (mCRPC) progressing on/after one line of NAH will be randomized to receive radium-223 dichloride
  Intervention: Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
• Active Comparator: Arm B
  Participants 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)
  Intervention: Drug: NAH therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 16, 2020): 696
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 25, 2024
• Estimated Primary Completion Date: April 25, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bayer Clinical Trials Contact; (+)1-888-84 22937; clinical-trials-contact@bayer.com

• Listed Location Countries: Australia, Austria, Czechia, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Lithuania, Poland, Russian Federation, Singapore, Spain, Taiwan, Turkey, United Kingdom

Administrative Information

• NCT Number: NCT04597125
• Other Study ID Numbers: 20510; 2019-000476-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

Plan Description

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Bayer
• Verification Date: March 2021