Radiation Medication (Radium-223 Dichloride) Versus Radium-223 Dichloride Plus Radiation Enhancing Medication (M3814) Versus Radium-223 Dichloride Plus M3814 Plus Avelumab (a Type of Immunotherapy) for Advanced Prostate Cancer Not Responsive to Hormonal Therapy
NCT ID: NCT04071236
Last Updated: 2026-02-04
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Clinical Phase
PHASE1/PHASE2
Total Enrollment
90 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-10-14
Study Completion Date
2026-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This phase I/II trial studies the best dose of M3814 when given together with radium-223 dichloride or with radium-223 dichloride and avelumab and to see how well they work in treating patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as radium-223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to find out the better treatment between radium-223 dichloride alone, radium-223 dichloride in combination with M3814, or radium-223 dichloride in combination with both M3814 and avelumab, to lower the chance of prostate cancer growing or spreading in the bone, and if this approach is better or worse than the usual approach for advanced prostate cancer not responsive to hormonal therapy.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms
NCT02043678
Prostatic Neoplasms
COMPLETED
PHASE3
Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma
NCT03436654
Prostate Cancer
ACTIVE_NOT_RECRUITING
PHASE2
Antiandrogen Therapy, Abiraterone Acetate, and Prednisone With or Without Neutron Radiation Therapy in Treating Patients With Prostate Cancer
NCT03649841
Castration-Sensitive Prostate Carcinoma
Metastatic Malignant Neoplasm in the Bone
Metastatic Prostate Carcinoma
+5 more
TERMINATED
PHASE2
Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging
NCT04423211
Biochemically Recurrent Prostate Carcinoma
Metastatic Prostate Carcinoma
Prostate Adenocarcinoma
+1 more
RECRUITING
PHASE3
A Study of Shorter Course Hormone Therapy and Radiation for High-risk Prostate Cancer
NCT05100472
Prostate Cancer
ACTIVE_NOT_RECRUITING
PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of peposertib (M3814) in combination with radium-223 dichloride or in combination with radium-223 dichloride and avelumab in patients with advanced metastatic castrate-resistant prostate cancer (mCRPC) based on dose limiting toxicities (DLTs) in the doublet or triplet combinations. (Phase 1) II. Radiographic progression free survival (rPFS) will be evaluated based on both skeletal and extraskeletal progression following Prostate Cancer Working Group 3 (PCWG3) methodology. (Phase 2)
SECONDARY OBJECTIVES:
I. To determine the time to the first symptomatic skeletal event \[SSE\]. II. To determine the safety of radium-223 dichloride, M3814, and avelumab combination treatment.
III. To observe and record anti-tumor activity. IV. To evaluate progression free survival (PFS) and overall survival (OS). V. To evaluate symptomatic skeletal events (SSE) per standardized case report form (CRF) distinguishing between pathologic and non-pathogenic fractures.
VI. To explore patient-reported symptomatic adverse events (AE) for tolerability of each treatment arm.
VII. To examine the radium-223 dichloride bio-distribution and absorbed dose in each bone metastatic lesions as well as elsewhere in the body including critical organs using dosimetry.
EXPLORATORY OBJECTIVES:
I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned, and Ib. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.
III. To bank plasma and peripheral immune cells from patients to assess predictive biomarkers of response at the Experimental Therapeutics Clinical Trials Network (ETCTN) biorepository at Nationwide Children's Hospital.
IV. To correlate change in level of total alkaline phosphatase, bone-specific alkaline phosphatase, and serum osteocalcin to rPFS and OS.
OUTLINE: This is a phase I, dose-escalation study of peposertib, followed by a phase II study. Patients are randomized to 1 of 3 arms.
ARM A: Patients receive radium-223 dichloride intravenously (IV) over 1 minute on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
ARM B: Patients receive radium-223 dichloride as in Arm A and peposertib orally (PO) once daily (QD) or twice daily (BID) on days 3-26. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
ARM C: Patients receive radium-223 dichloride IV as in Arm A and peposertib PO QD or BID as in Arm B. Patients also receive avelumab IV over 60 minutes on days 1 and 15 of cycles 2-6. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years.
I. To determine the maximum tolerated dose (MTD) of peposertib (M3814) in combination with radium-223 dichloride or in combination with radium-223 dichloride and avelumab in patients with advanced metastatic castrate-resistant prostate cancer (mCRPC) based on dose limiting toxicities (DLTs) in the doublet or triplet combinations. (Phase 1) II. Radiographic progression free survival (rPFS) will be evaluated based on both skeletal and extraskeletal progression following Prostate Cancer Working Group 3 (PCWG3) methodology. (Phase 2)
SECONDARY OBJECTIVES:
I. To determine the time to the first symptomatic skeletal event \[SSE\]. II. To determine the safety of radium-223 dichloride, M3814, and avelumab combination treatment.
III. To observe and record anti-tumor activity. IV. To evaluate progression free survival (PFS) and overall survival (OS). V. To evaluate symptomatic skeletal events (SSE) per standardized case report form (CRF) distinguishing between pathologic and non-pathogenic fractures.
VI. To explore patient-reported symptomatic adverse events (AE) for tolerability of each treatment arm.
VII. To examine the radium-223 dichloride bio-distribution and absorbed dose in each bone metastatic lesions as well as elsewhere in the body including critical organs using dosimetry.
EXPLORATORY OBJECTIVES:
I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned, and Ib. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.
III. To bank plasma and peripheral immune cells from patients to assess predictive biomarkers of response at the Experimental Therapeutics Clinical Trials Network (ETCTN) biorepository at Nationwide Children's Hospital.
IV. To correlate change in level of total alkaline phosphatase, bone-specific alkaline phosphatase, and serum osteocalcin to rPFS and OS.
OUTLINE: This is a phase I, dose-escalation study of peposertib, followed by a phase II study. Patients are randomized to 1 of 3 arms.
ARM A: Patients receive radium-223 dichloride intravenously (IV) over 1 minute on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
ARM B: Patients receive radium-223 dichloride as in Arm A and peposertib orally (PO) once daily (QD) or twice daily (BID) on days 3-26. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
ARM C: Patients receive radium-223 dichloride IV as in Arm A and peposertib PO QD or BID as in Arm B. Patients also receive avelumab IV over 60 minutes on days 1 and 15 of cycles 2-6. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Metastatic Castration-Resistant Prostate Carcinoma
Metastatic Malignant Neoplasm in the Bone
Metastatic Malignant Neoplasm in the Lymph Nodes
Stage IVB Prostate Cancer AJCC v8
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A (radium-223 dichloride)
Patients receive radium-223 dichloride IV over 1 minute on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
Group Type
ACTIVE_COMPARATOR
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Scan
Intervention Type
PROCEDURE
Undergo bone scan
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Radium Ra 223 Dichloride
Intervention Type
RADIATION
Given IV
Arm B (radium-223 dichloride, nedisertib)
Patients receive radium-223 dichloride as in Arm A and peposertib PO or BID on days 3-26. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
Group Type
ACTIVE_COMPARATOR
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Scan
Intervention Type
PROCEDURE
Undergo bone scan
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Peposertib
Intervention Type
DRUG
Given PO
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Radium Ra 223 Dichloride
Intervention Type
RADIATION
Given IV
Arm C (radium-223 dichloride, nedisertib, avelumab)
Patients receive radium-223 dichloride IV as in Arm A and peposertib PO QD or BID as in Arm B. Patients also receive avelumab IV over 60 minutes on days 1 and 15 of cycles 2-6. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone scan, and CT or MRI throughout the study.
Group Type
EXPERIMENTAL
Avelumab
Intervention Type
DRUG
Given IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Scan
Intervention Type
PROCEDURE
Undergo bone scan
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Peposertib
Intervention Type
DRUG
Given PO
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Radium Ra 223 Dichloride
Intervention Type
RADIATION
Given IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Avelumab
Given IV
Intervention Type
DRUG
Biospecimen Collection
Undergo blood sample collection
Intervention Type
PROCEDURE
Bone Scan
Undergo bone scan
Intervention Type
PROCEDURE
Computed Tomography
Undergo CT
Intervention Type
PROCEDURE
Magnetic Resonance Imaging
Undergo MRI
Intervention Type
PROCEDURE
Peposertib
Given PO
Intervention Type
DRUG
Questionnaire Administration
Ancillary studies
Intervention Type
OTHER
Radium Ra 223 Dichloride
Given IV
Intervention Type
RADIATION
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Bavencio
MSB 0010718C
MSB-0010718C
MSB0010718C
Biological Sample Collection
Biospecimen Collected
Specimen Collection
Bone Scintigraphy
CAT
CAT Scan
Computed Axial Tomography
Computerized Axial Tomography
Computerized axial tomography (procedure)
Computerized Tomography
Computerized Tomography (CT) scan
CT
CT Scan
Diagnostic CAT Scan
Diagnostic CAT Scan Service Type
tomography
Magnetic Resonance
Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging (procedure)
Magnetic Resonance Imaging Scan
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
MR
MR Imaging
MRI
MRI Scan
MRIs
NMR Imaging
NMRI
Nuclear Magnetic Resonance Imaging
sMRI
Structural MRI
3-Pyridazinemethanol, alpha-(2-Chloro-4-fluoro-5-(7-(4-morpholinyl)-4-quinazolinyl)phenyl)-6-methoxy-, (alphaS)-
M 3814
M-3814
M3814
MSC 2490484A
MSC-2490484A
MSC2490484A
Nedisertib
Alpharadin
BAY 88-8223
BAY88-8223
Radium 223 Dichloride
RADIUM RA-223 DICHLORIDE
Radium-223 Chloride
Radium-223 Dichloride
Xofigo
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* PHASE 1: Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* PHASE 2: ECOG performance status =\< 2 (Karnofsky \>= 60%)
* Unless a patient has had orchiectomy by surgery, the patient is expected to be on antiandrogen therapy (ADT) for "medical castration". ADT needs to be maintained throughout the study. Testosterone level should be checked, and kept consistently lower than 50 ng/dL, similar to that obtained with bilateral orchiectomy
* Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by 99mTC bone scintigraphy. One or more lymph node metastases allowed, but not mandatory. Lymph node metastases in each individually must measure less than 3 cm in the longest dimension. Visible visceral organ metastases are not allowed. A diagnosis of prostate cancer must have been histologically confirmed at any time point
* Baseline prostatic specific antigen (PSA) level of 1 ng/mL or higher with evidence of progressively increasing PSA values (two consecutive increases over the previous reference value)
* Progression after at least one of the following: abiraterone, enzalutamide, apalutamide, darolutamide, or taxane chemotherapy (docetaxel, cabazitaxel). There is no maximum number of prior therapies. Prior immunotherapies (for example, Sipuleucel-T or pembrolizumab) do not exclude the patient from participation
* Age \>= 18 years. Castrate-resistant prostate cancer (CRPC) affects older adults and is rarely encountered in children and adolescents
* Life expectancy \>= 6 months
* Albumin \> 2.5 mg/dL
* Hemoglobin \> 9 g/dL
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (with the exception of \< 3 mg/dL for patients with Gilbert's disease)
* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
* Creatinine =\< 1.5 x institutional ULN OR
* Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better
* Concomitant use of physiologic corticosteroids is allowed
* Concomitant use of bisphosphonates is allowed (use of bone health agents is mandatory - either denosumab \[preferred\] or bisphosphonates)
* The effects of radium-223 dichloride, M3814, and avelumab on the developing human fetus are unknown. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of Radium-223 dichloride, M3814, and avelumab administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
* Patients must be able to swallow orally administered medication
* Patients with asymptomatic, treated brain metastases are permitted if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or CT scan) during the screening period
* PHASE 2: ECOG performance status =\< 2 (Karnofsky \>= 60%)
* Unless a patient has had orchiectomy by surgery, the patient is expected to be on antiandrogen therapy (ADT) for "medical castration". ADT needs to be maintained throughout the study. Testosterone level should be checked, and kept consistently lower than 50 ng/dL, similar to that obtained with bilateral orchiectomy
* Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by 99mTC bone scintigraphy. One or more lymph node metastases allowed, but not mandatory. Lymph node metastases in each individually must measure less than 3 cm in the longest dimension. Visible visceral organ metastases are not allowed. A diagnosis of prostate cancer must have been histologically confirmed at any time point
* Baseline prostatic specific antigen (PSA) level of 1 ng/mL or higher with evidence of progressively increasing PSA values (two consecutive increases over the previous reference value)
* Progression after at least one of the following: abiraterone, enzalutamide, apalutamide, darolutamide, or taxane chemotherapy (docetaxel, cabazitaxel). There is no maximum number of prior therapies. Prior immunotherapies (for example, Sipuleucel-T or pembrolizumab) do not exclude the patient from participation
* Age \>= 18 years. Castrate-resistant prostate cancer (CRPC) affects older adults and is rarely encountered in children and adolescents
* Life expectancy \>= 6 months
* Albumin \> 2.5 mg/dL
* Hemoglobin \> 9 g/dL
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (with the exception of \< 3 mg/dL for patients with Gilbert's disease)
* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
* Creatinine =\< 1.5 x institutional ULN OR
* Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better
* Concomitant use of physiologic corticosteroids is allowed
* Concomitant use of bisphosphonates is allowed (use of bone health agents is mandatory - either denosumab \[preferred\] or bisphosphonates)
* The effects of radium-223 dichloride, M3814, and avelumab on the developing human fetus are unknown. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of Radium-223 dichloride, M3814, and avelumab administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
* Patients must be able to swallow orally administered medication
* Patients with asymptomatic, treated brain metastases are permitted if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or CT scan) during the screening period
Exclusion Criteria
* Active autoimmune conditions or patients on chronic immunosuppression due to underlying autoimmune condition
* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* Patients who have had previous hemibody external radiation
* Patients who have imminent/established spinal cord compression, pathological fracture in weight bearing bones or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on trial
* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to radium-223 dichloride, M3814, or avelumab
* Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to study treatment are ineligible.
* Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
* Medications or substances that are strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first M3814 dose.
* Drugs mainly metabolized by CYP3A with a narrow therapeutic index (as judged by the Investigator or authorized designee) must be discontinued at least 1 day prior to first M3814 dose.
* Note: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently- updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the- counter medicine or herbal product.
* Radium-223 dichloride should not be given concurrently with abiraterone plus prednisone/prednisolone
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Patients must not have an active infection requiring systemic treatment
* Patients must not use immunosuppressive medication =\< 7 days of registration, EXCEPT for the following:
* Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
* Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Patients who cannot discontinue concomitant H2 blockers or proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued \>= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
* Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
* Patients with a known history or present osteonecrosis of the jaw
* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* Patients who have had previous hemibody external radiation
* Patients who have imminent/established spinal cord compression, pathological fracture in weight bearing bones or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on trial
* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to radium-223 dichloride, M3814, or avelumab
* Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to study treatment are ineligible.
* Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
* Medications or substances that are strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first M3814 dose.
* Drugs mainly metabolized by CYP3A with a narrow therapeutic index (as judged by the Investigator or authorized designee) must be discontinued at least 1 day prior to first M3814 dose.
* Note: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently- updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the- counter medicine or herbal product.
* Radium-223 dichloride should not be given concurrently with abiraterone plus prednisone/prednisolone
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Patients must not have an active infection requiring systemic treatment
* Patients must not use immunosuppressive medication =\< 7 days of registration, EXCEPT for the following:
* Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
* Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Patients who cannot discontinue concomitant H2 blockers or proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued \>= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
* Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
* Patients with a known history or present osteonecrosis of the jaw
Minimum Eligible Age
18 Years
Eligible Sex
MALE
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Hiram A Gay
Role: PRINCIPAL_INVESTIGATOR
Yale University Cancer Center LAO
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Site Status
RECRUITING
Los Angeles General Medical Center
Los Angeles, California, United States
Site Status
RECRUITING
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Site Status
RECRUITING
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Site Status
RECRUITING
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Site Status
ACTIVE_NOT_RECRUITING
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
Site Status
RECRUITING
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
Site Status
RECRUITING
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Site Status
RECRUITING
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Site Status
RECRUITING
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
Site Status
RECRUITING
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Site Status
RECRUITING
Emory University Hospital Midtown
Atlanta, Georgia, United States
Site Status
ACTIVE_NOT_RECRUITING
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Site Status
ACTIVE_NOT_RECRUITING
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Site Status
ACTIVE_NOT_RECRUITING
University of Kansas Clinical Research Center
Fairway, Kansas, United States
Site Status
ACTIVE_NOT_RECRUITING
University of Kansas Cancer Center
Kansas City, Kansas, United States
Site Status
ACTIVE_NOT_RECRUITING
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, United States
Site Status
ACTIVE_NOT_RECRUITING
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
Site Status
ACTIVE_NOT_RECRUITING
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Site Status
RECRUITING
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Site Status
SUSPENDED
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Site Status
RECRUITING
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Site Status
RECRUITING
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, United States
Site Status
ACTIVE_NOT_RECRUITING
Washington University School of Medicine
St Louis, Missouri, United States
Site Status
RECRUITING
Siteman Cancer Center-South County
St Louis, Missouri, United States
Site Status
RECRUITING
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States
Site Status
ACTIVE_NOT_RECRUITING
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Site Status
ACTIVE_NOT_RECRUITING
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Site Status
RECRUITING
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Site Status
RECRUITING
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Site Status
ACTIVE_NOT_RECRUITING
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Site Status
SUSPENDED
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
United States
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Site Public Contact
Role: primary
323-865-0451
Site Public Contact
Role: primary
954-461-2180
Site Public Contact
Role: primary
305-243-2647
Site Public Contact
Role: primary
305-243-2647
Site Public Contact
Role: primary
305-243-2647
Site Public Contact
Role: primary
305-243-2647
Site Public Contact
Role: primary
305-243-2647
Site Public Contact
Role: primary
859-257-3379
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2019-05620
Identifier Type: REGISTRY
Identifier Source: secondary_id
202006062
Identifier Type: -
Identifier Source: secondary_id
10301
Identifier Type: OTHER
Identifier Source: secondary_id
10301
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2019-05620
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Study of Abiraterone Acetate or Enzalutamide, Atezolizumab, GnRH Analog and Radiation Therapy in Men With Newly Diagnosed Hormone-sensitive Prostate Cancer
NCT04262154
ACTIVE_NOT_RECRUITING
PHASE2
Study Evaluating the Addition of Pembrolizumab to Radium-223 in mCRPC
NCT03093428
COMPLETED
PHASE2
Comparison of High-Dose Rate Brachytherapy and Stereotactic Ablative Radiotherapy as Monotherapy for the Treatment of Localized Prostate Cancer
NCT04253483
ACTIVE_NOT_RECRUITING
PHASE2
Brachytherapy in Treating Patients With Recurrent Prostate Cancer
NCT00005939
UNKNOWN
PHASE1/PHASE2
Clonal Emergence and Regression During Radium-223 Therapy for Metastatic Prostate Cancer
NCT03677076
COMPLETED
Radium Ra 223 Dichloride, Hormone Therapy and Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Prostate Cancer
NCT03361735
ACTIVE_NOT_RECRUITING
PHASE2
Safety and Tolerability of Atezolizumab (ATZ) in Combination With Radium-223 Dichloride (R-223-D) in Metastatic Castrate-Resistant Prostate Cancer (CRPC) Progressed Following Treatment With an Androgen Pathway Inhibitor
NCT02814669
COMPLETED
PHASE1
Chemotherapy With or Without Biological Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy
NCT00005847
COMPLETED
PHASE2
Avelumab Plus 2nd-generation ADT in African American Subjects With mCRPC
NCT03770455
TERMINATED
PHASE2
Phase IB Trial of Radium-223 and Niraparib in Patients With Castrate Resistant Prostate Cancer (NiraRad)
NCT03076203
COMPLETED
PHASE1
Stereotactic Body Radiation Therapy Plus Immediate or Delayed Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy or Salvage Radiation Therapy for the Treatment of Prostate Cancer, DIVINE Trial
NCT06378866
RECRUITING
PHASE2
Androgen Ablation Therapy With or Without Niraparib After Radiation Therapy for the Treatment of High-Risk Localized or Locally Advanced Prostate Cancer
NCT04947254
RECRUITING
PHASE2
A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer
NCT03748641
ACTIVE_NOT_RECRUITING
PHASE3
Androgen Suppression Plus Radiation Therapy in Treating Patients With Prostate Cancer
NCT00006359
COMPLETED
PHASE2
Standard Dose Versus High Dose and Versus Extended Standard Dose Radium-223 Dichloride in Castration-resistant Prostate Cancer Metastatic to the Bone
NCT02023697
COMPLETED
PHASE2
ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC)
NCT02325557
COMPLETED
PHASE1/PHASE2
A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT03431350
ACTIVE_NOT_RECRUITING
PHASE2
A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)
NCT02034552
COMPLETED
PHASE2
A Study to Test Radium-223 With Docetaxel in Patients With Prostate Cancer
NCT03574571
ACTIVE_NOT_RECRUITING
PHASE3
Hormone Therapy Followed By Internal Radiation Therapy in Treating Patients With Locally Recurrent Prostate Cancer
NCT00032006
COMPLETED
PHASE2
Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer
NCT05915442
RECRUITING
PHASE2
Stereotactic Body Radiotherapy (SBRT) for Localized Prostate Cancer
NCT04489745
UNKNOWN
PHASE2
Phase I/II Trial of Pembrolizumab and Androgen-receptor Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer
NCT04946370
ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
Testing the Safety of Different Doses of Olaparib Given Radium-223 for Men With Advanced Prostate Cancer With Bone Metastasis
NCT03317392
ACTIVE_NOT_RECRUITING
PHASE1/PHASE2