Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2017-01920 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 10096 | Other Identifier | Yale University Cancer Center LAO | |
| 10096 | Other Identifier | CTEP | |
| UM1CA186689 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This phase I/II trial studies the best dose and side effects of olaparib and how well it works with radium Ra 223 dichloride in treating patients with castration-resistant prostate cancer that has spread to the bone and other places in the body (metastatic). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radioactive drugs, such as radium Ra 223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Giving olaparib and radium Ra 223 dichloride may help treat patients with castration-resistant prostate cancer.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of olaparib in combination with radium Ra 223 dichloride (radium-223). (Phase I) II. Evaluate the radiographic progression-free survival (rPFS). (Phase II)
SECONDARY OBJECTIVES:
I. Evaluate safety and tolerability as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
II. To evaluate rPFS as stratified by disease extent (=< 20 or > 20 bone lesions) and prior docetaxel use (yes or no).
III. Evaluate rPFS in patients harboring or lacking evidence of homologous recombination deficiency (HRD).
IV. Evaluate rPFS in patients based on prior abiraterone and/or next generation androgen receptor (AR) antagonist (enzalutamide, apalutamide, darolutamide or other agent) use (yes versus no) for either hormone sensitive or castration resistant prostate cancer (CRPC).
V. Evaluate prostate specific antigen (PSA) response rate as defined by >= 50% decline in PSA from baseline.
VI. Evaluate total alkaline phosphatase response defined as a reduction of >= 30% from the baseline value, confirmed >= 4 weeks later.
VII. Evaluate time to PSA progression as defined by Prostate Cancer Clinical Trials Working Group (PCTWG) 3 criteria.
VIII. Evaluate radiographic objective response rate as defined by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.
IX. Evaluate time to increase in the total alkaline phosphatase (ALP) level defined as an increase of >= 25% from baseline at >= 12 weeks, in patients with no decrease from baseline, or as an increase of >= 25% above the nadir, confirmed >= 3 weeks later, in patients with an initial decrease from baseline.
X. Evaluate time to first subsequent anti-cancer therapy (including AR signaling agents, cytotoxic chemotherapy, immunotherapy, or investigational agents) or death.
XI. Evaluate time to first symptomatic skeletal event (SSE). XII. Evaluate overall survival (OS).
EXPLORATORY OBJECTIVES:
I. Evaluate impact on quality of life (QOL) as determined by Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and Brief Pain Inventory (BPI).
II. Estimate the frequency of mutations in the deoxyribonucleic acid (DNA) repair pathway in patients with metastatic castration-resistant prostate cancer (CRPC) as determine by Oncopanel testing and by whole exome sequencing (WES).
III. Characterize changes in ribonucleic acid (RNA) expression of DNA repair genes and immune markers by whole transcriptome sequencing (WTS) in each arm.
IV. Characterize changes in immune cell, T-cell receptor (TCR), and B-cell (BCR) receptor repertoire at baseline, during treatment, and at progression in each arm.
V. Evaluate changes in lactate dehydrogenase (LDH) in patients each treatment arm.
VI. Assess the prevalence of germline mutations in homologous recombination genes in all enrolled patients.
VII. Correlate homologous recombination gene germline mutation status with PSA response by treatment arm.
VIII. Evaluate family history of cancers in the study population and correlate family cancer history with germline mutation status.
IX. Correlate presence or absence of RAD51 with somatic and germline homologous recombination gene mutation status, PSA response, and PFS between treatment arms.
X. Evaluate the changes in whole genome sequencing (WGS) of plasma cell-free circulating DNA (cfDNA) based patient-tumor specific signature at baseline, on treatment, and at progression.
XI. Evaluate tumor mutation burden (TMB) and tumor mutational signature in plasma cfDNA at baseline and correlate to tumor tissue TMB and mutational signature.
OUTLINE: This is a phase I, dose-escalation study of olaparib followed by a phase II study.
PHASE I: Patients receive radium Ra 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 also receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) as well as blood sample collection and a tissue biopsy during screening and on study.
PHASE II: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive radium Ra 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 also receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study.
ARM II: Patients receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study.
After completion of study treatment, patients are followed up every 6 months for 2 years.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase I (radium Ra 223 dichloride, olaparib) | Experimental | Patients in Phase I receive radium Ra 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 also receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. |
|
| Phase II Arm I (radium Ra 223 dichloride, olaparib) | Experimental | Patients in Phase II Arm I receive radium Ra 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 also receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. |
|
| Phase II Arm II (radium Ra 223 dichloride) | Experimental | Patients in Phase 2 Arm II receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biopsy Procedure | Procedure | Undergo tissue biopsy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase I: Maximum Tolerated Dose | Determine the maximum tolerated dose (MTD) of olaparib in combination with radium Ra 223 dichloride (radium-223). (Phase I) | 56 days |
| Phase II: Radiographic Progression-free Survival (rPFS) | Radiographic progression is defined by Prostate Cancer Working Group 3 criteria for bone metastases and RECIST version 1.1 for non-bone metastases. Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. A stratified Cox proportional hazards regression model will estimate the rPFS treatment hazard ratio with 80% 2-sided confidence intervals (CIs). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", | From randomization to date of radiographic progression or death due to any cause, whichever occurs first, or censored at the date of last disease assessment. Up to approximately 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Phase II: rPFS in Patients Without Prior Docetaxel | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Up to approximately 2 years after randomization |
| Phase II: rPFS in Patients With Prior Docetaxel |
| Measure | Description | Time Frame |
|---|---|---|
| Phase II: rPFS in Patients Without Homologous Recombination Deficiency | rPFS in patients without homologous recombination deficiency | Up to approximately 2 years after randomization |
| Phase II: rPFS in Patients With Homologous Recombination Deficiency |
Inclusion Criteria:
Participants must be male aged >= 18 years of age
Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate
Participants must have castrate levels of serum testosterone < 50 ng/dL
Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist; participants receiving prior docetaxel abiraterone, or next generation AR antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease are permitted
Participants must have progressive disease as defined by any of the following:
Participants must have >= 2 bone metastases by radiographic imaging and at least 1 lesion which has not been treated with prior radiation therapy
Participants must have tumor accessible for biopsy and be agreeable to baseline tumor biopsy; a metastatic focus is preferred but if not available and prostate is still intact prostate biopsy can be performed
Availability at the study site of formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens, when available
Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
White blood cell count (WBC) >= 3,000/mcL (within 28 days prior to administration of study treatment)
Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days prior to administration of study treatment)
Platelets >= 100,000/mcL (within 28 days prior to administration of study treatment)
Hemoglobin >= 10 g/dL (transfusions permitted) (within 28 days prior to administration of study treatment)
Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment); for subjects with Gilbert's disease =< 3.0 mg/dL
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to administration of study treatment)
Creatinine clearance >= 51 ml/min as defined by Cockcroft-Gault equation (within 28 days prior to administration of study treatment)
Participants should be receiving an osteoclast targeting agent including either bisphosphonates or denosumab except in patients with contraindications as determined by the treating investigator including:
The effects of olaparib and radium-223 on the developing human fetus are unknown; for this reason, men treated or enrolled on this protocol must agree to use adequate contraception and avoid sperm donation prior to the study, for the duration of study participation, and three months after discontinuation of olaparib and radium-223 administration
Human immunodeficiency virus (HIV)-positive with negative viral loads on stable antiretroviral regimen and CD4 count > 250 are eligible
Ability to understand and the willingness to sign a written informed consent document; patients with impaired decision-making who have a legal guardian (e.g., spouse) able to make informed decisions on behalf of the patient are eligible
Patients must be able to tolerate oral medications by mouth and not have a gastrointestinal illness that would preclude absorption of olaparib
Exclusion Criteria:
Pathology consistent with small cell carcinoma of the prostate
Presence of visceral metastases (liver, lung, brain, etc.) or malignant lymphadenopathy exceeding 4 centimeters (cm) in short diameter
Prior treatment with radium-223
Prior treatment with olaparib or other PARPi
Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation; treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation; treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation; treatment with enzalutamide within 4 weeks of treatment initiation
Prior hemibody external radiotherapy
Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation
Participants who are receiving any other investigational agents
Imminent or established spinal cord compression based on clinical and/or imaging findings
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring need for intravenous anti-microbials, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Clinically significant medical condition defined as:
Major surgery within 4 weeks of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible
History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
Patient unable to swallow orally administered medication
History of bowel obstruction within 1 month of study treatment
History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the 3 months of study treatment
History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or radium-223
Participants receiving strong CYP3A4/5 inducers or inhibitors are ineligible; dihydropyridine calcium-channel blockers are permitted for management of hypertension; the required washout period prior to starting olaparib is 2 weeks for CYP3A inhibitors; the required washout period prior to starting olaparib is 4 weeks for enzalutamide or phenobarbital and 3 weeks for other CYP3A inducers
Patients with known active hepatitis (i.e. hepatitis B or C) infection
Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
Patient having received prior allogenic bone marrow transplant or double umbilical cord blood transplantation
Individuals with a history of a different malignancy are ineligible except for the following circumstances:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Rana R McKay | Yale University Cancer Center LAO | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Moores Cancer Center | La Jolla | California | 92093 | United States | ||
| University of California Davis Comprehensive Cancer Center |
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Phase I Radium223+Olaparib Dose Level 1 | Dose level I: Radium223 plus olaparib 200 mg orally twice daily |
| FG001 | Phase I Radium223+Olaparib Dose Level 2 | Dose level II: Radium223 plus olaparib 300 mg orally twice daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 5, 2025 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Biospecimen Collection | Procedure | Undergo blood sample collection |
|
|
| Computed Tomography | Procedure | Undergo CT |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Magnetic Resonance Imaging | Procedure | Undergo MRI |
|
|
| Olaparib | Drug | Given PO |
|
|
| Quality-of-Life Assessment | Other | Ancillary studies |
|
|
| Radium Ra 223 Dichloride | Radiation | Given IV |
|
|
Median rPFS will be estimated using the Kaplan-Meier method by treatment arm.
| Up to approximately 2 years after randomization |
| Phase II: rPFS in Patients With ≤ 20 Bone Lesions | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Up to approximately 2 years after randomization |
| Phase II: rPFS in Patients With > 20 Bone Lesions | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Up to approximately 2 years after randomization |
| Phase II: Overall Survival (OS) | Phase II: Median OS will be estimated using the method of Kaplan-Meier. | From randomization to the date of death due to any cause, or censored at the date of last follow-up, assessed up to 3.5 years |
rPFS in patients with homologous recombination deficiency
| Up to approximately 2 years after randomization |
| Phase II: Prostate Specific Antigen (PSA) Response | Number of participants with prostate specific antigen (PSA) response defined as PSA ≥50% decrease from baseline | Up to approximately 2 years after randomization |
| Phase II: Alkaline Phosphatase (ALP) Response | Alkaline phosphatase (ALP) response defined as ≥30% decrease from baseline. | Up to approximately 2 years after randomization |
| Phase II: Symptomatic Skeletal Event (SSE) | Symptomatic skeletal event (SSE) defined as pathologic bone fracture, spinal cord compression, or radiation therapy to bone. | Up to approximately 2 years after randomization |
| Phase II: Incidence of Grade 3 or Higher Treatment Related Adverse Events (TrAE) | Incidence of grade 3 or higher treatment related adverse events (TrAE) | Up to approximately 2 years after randomization |
| Sacramento |
| California |
| 95817 |
| United States |
| Smilow Cancer Center/Yale-New Haven Hospital | New Haven | Connecticut | 06510 | United States |
| Yale University | New Haven | Connecticut | 06520 | United States |
| University of Kansas Clinical Research Center | Fairway | Kansas | 66205 | United States |
| University of Kansas Cancer Center | Kansas City | Kansas | 66160 | United States |
| University of Kansas Cancer Center-Overland Park | Overland Park | Kansas | 66210 | United States |
| University of Kansas Hospital-Westwood Cancer Center | Westwood | Kansas | 66205 | United States |
| University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | 21201 | United States |
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Siteman Cancer Center at Saint Peters Hospital | City of Saint Peters | Missouri | 63376 | United States |
| Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri | 63141 | United States |
| University of Kansas Cancer Center - North | Kansas City | Missouri | 64154 | United States |
| University of Kansas Cancer Center - Lee's Summit | Lee's Summit | Missouri | 64064 | United States |
| University of Kansas Cancer Center at North Kansas City Hospital | North Kansas City | Missouri | 64116 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Siteman Cancer Center-South County | St Louis | Missouri | 63129 | United States |
| Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | 08903 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Ohio State University Comprehensive Cancer Center | Columbus | Ohio | 43210 | United States |
| University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | 15232 | United States |
| University of Wisconsin Carbone Cancer Center - University Hospital | Madison | Wisconsin | 53792 | United States |
| FG002 | Phase II Arm I (Radium Ra 223 Dichloride, Olaparib) | Patients receive radium Ra 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 also receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV |
| FG003 | Phase II Arm II (Radium Ra 223 Dichloride) | Patients receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase I Radium223+Olaparib Dose Level 1 | Dose level I: Radium223 at 55 kBq/kg q4w plus olaparib 200 mg orally twice daily |
| BG001 | Phase I Radium223+Olaparib Dose Level 2 | Dose level II: Radium223 at 55 kBq/kg q4w plus olaparib 300 mg orally twice daily |
| BG002 | Phase II Arm I (Radium Ra 223 Dichloride, Olaparib) | Patients receive radium Ra 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 also receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV |
| BG003 | Phase II Arm II (Radium Ra 223 Dichloride) | Patients receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Previous use of androgen receptor pathway inhibitors | Count of Participants | Participants |
| ||||||||||||||||
| Previous use of any chemotherapy | Count of Participants | Participants |
| ||||||||||||||||
| Previous use of docetaxel | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase I: Maximum Tolerated Dose | Determine the maximum tolerated dose (MTD) of olaparib in combination with radium Ra 223 dichloride (radium-223). (Phase I) | Posted | Number | mg | 56 days |
|
|
| ||||||||||||||||||||||||||||||
| Primary | Phase II: Radiographic Progression-free Survival (rPFS) | Radiographic progression is defined by Prostate Cancer Working Group 3 criteria for bone metastases and RECIST version 1.1 for non-bone metastases. Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. A stratified Cox proportional hazards regression model will estimate the rPFS treatment hazard ratio with 80% 2-sided confidence intervals (CIs). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", | Posted | Median | 95% Confidence Interval | months | From randomization to date of radiographic progression or death due to any cause, whichever occurs first, or censored at the date of last disease assessment. Up to approximately 2 years |
| |||||||||||||||||||||||||||||||
| Secondary | Phase II: rPFS in Patients Without Prior Docetaxel | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Posted | Median | 95% Confidence Interval | months | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Secondary | Phase II: rPFS in Patients With Prior Docetaxel | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Posted | Median | 95% Confidence Interval | months | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Secondary | Phase II: rPFS in Patients With ≤ 20 Bone Lesions | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Posted | Median | 95% Confidence Interval | months | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Secondary | Phase II: rPFS in Patients With > 20 Bone Lesions | Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. | Posted | Median | 95% Confidence Interval | months | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Secondary | Phase II: Overall Survival (OS) | Phase II: Median OS will be estimated using the method of Kaplan-Meier. | Posted | Median | 95% Confidence Interval | months | From randomization to the date of death due to any cause, or censored at the date of last follow-up, assessed up to 3.5 years |
| |||||||||||||||||||||||||||||||
| Other Pre-specified | Phase II: rPFS in Patients Without Homologous Recombination Deficiency | rPFS in patients without homologous recombination deficiency | Posted | Median | 95% Confidence Interval | months | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Other Pre-specified | Phase II: rPFS in Patients With Homologous Recombination Deficiency | rPFS in patients with homologous recombination deficiency | Posted | Median | 95% Confidence Interval | months | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Other Pre-specified | Phase II: Prostate Specific Antigen (PSA) Response | Number of participants with prostate specific antigen (PSA) response defined as PSA ≥50% decrease from baseline | Posted | Count of Participants | Participants | Up to approximately 2 years after randomization |
| ||||||||||||||||||||||||||||||||
| Other Pre-specified | Phase II: Alkaline Phosphatase (ALP) Response | Alkaline phosphatase (ALP) response defined as ≥30% decrease from baseline. | Posted | Count of Participants | Participants | Up to approximately 2 years after randomization |
| ||||||||||||||||||||||||||||||||
| Other Pre-specified | Phase II: Symptomatic Skeletal Event (SSE) | Symptomatic skeletal event (SSE) defined as pathologic bone fracture, spinal cord compression, or radiation therapy to bone. | Posted | Number | 95% Confidence Interval | Percent of participants | Up to approximately 2 years after randomization |
| |||||||||||||||||||||||||||||||
| Other Pre-specified | Phase II: Incidence of Grade 3 or Higher Treatment Related Adverse Events (TrAE) | Incidence of grade 3 or higher treatment related adverse events (TrAE) | Posted | Number | events | Up to approximately 2 years after randomization |
|
Adverse events (AE) are assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5 by treatment arm, from enrollment until end of study visit, up to approximately 2.5 years after randomization. All-Cause Mortality monitored/assessed up to 3.5 years.
AE analyses include patients that actually receiving treatment. A serious AE (SAE) includes an AE that results in any of 1)death, 2)a life-threatening event, 3)inpatient hospitalization or prolonged hospitalization for ≥24 hours, 4)persistent/significant incapacity, or substantial disruption of the ability to conduct normal life functions, 5)a congenital anomaly or birth defect, 6)need for medical/surgical intervention to prevent any outcome above. Other AEs include non-SAE events.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase I Radium223+Olaparib Dose Level 1 | Dose level I: Radium223 at 55 kBq/kg q4w plus olaparib 200 mg orally twice daily | 6 | 6 | 4 | 6 | 6 | 6 |
| EG001 | Phase I Radium223+Olaparib Dose Level 2 | Dose level II: Radium223 at 55 kBq/kg q4w plus olaparib 300 mg orally twice daily | 3 | 6 | 2 | 6 | 6 | 6 |
| EG002 | Phase II Arm I (Radium Ra 223 Dichloride, Olaparib) | Patients receive radium Ra 223 dichloride IV at 55 kBq/kg 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 also receive olaparib 200 mg PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV | 38 | 61 | 39 | 59 | 59 | 59 |
| EG003 | Phase II Arm II (Radium Ra 223 Dichloride) | Patients receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV | 18 | 59 | 29 | 55 | 55 | 55 |
| EG004 | Phase II Arm I After Cross-over From Arm II (Radium Ra 223 Dichloride, Olaparib) | Patient initially assigned to Arm II will have the option to cross over to Arm I treatment at radiographic progression. Radium 223 IV at 55 kBq/kg up to 6 cycles. Olaparib 200 mg orally twice daily | 16 | 23 | 11 | 23 | 23 | 23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocyte count decreased | Investigations | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
| ||
| Non-cardiac chest pain | General disorders | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Spinal cord compression | Nervous system disorders | Systematic Assessment |
| ||
| Hematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Disease progression | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bone pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Asystole | Cardiac disorders | Systematic Assessment |
| ||
| Paroxysmal atrial tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Vision decreased | Eye disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Ascites | Gastrointestinal disorders | Systematic Assessment |
| ||
| Blood in the stool | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fecal incontinence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Death NOS | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Systematic Assessment |
| ||
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
| ||
| Fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Hip fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Spinal fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Weight loss | Investigations | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Buttock pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Intracranial hemorrhage | Nervous system disorders | Systematic Assessment |
| ||
| Presyncope | Nervous system disorders | Systematic Assessment |
| ||
| Delirium | Psychiatric disorders | Systematic Assessment |
| ||
| Urinary tract obstruction | Renal and urinary disorders | Systematic Assessment |
| ||
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hematoma | Vascular disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Lymphocyte count decreased | Investigations | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Weight loss | Investigations | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Blood lactate dehydrogenase increased | Investigations | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Edema limbs | General disorders | Systematic Assessment |
| ||
| Creatinine increased | Investigations | Systematic Assessment |
| ||
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
| ||
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Dysgeusia | Nervous system disorders | Systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Bone pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Insomnia | Psychiatric disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Blood bicarbonate decreased | Investigations | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Paresthesia | Nervous system disorders | Systematic Assessment |
| ||
| Hematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Hot flashes | Vascular disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
| ||
| Bruising | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| COVID-19 | Infections and infestations | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Muscle cramp | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Depression | Psychiatric disorders | Systematic Assessment |
| ||
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Systematic Assessment |
| ||
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
| ||
| Bloating | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gait disturbance | General disorders | Systematic Assessment |
| ||
| Non-cardiac chest pain | General disorders | Systematic Assessment |
| ||
| Hypermagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Anxiety | Psychiatric disorders | Systematic Assessment |
| ||
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Palpitations | Cardiac disorders | Systematic Assessment |
| ||
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fecal incontinence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Presyncope | Nervous system disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
| ||
| Sinus bradycardia | Cardiac disorders | Systematic Assessment |
| ||
| Vertigo | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Toothache | Gastrointestinal disorders | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Electrocardiogram QT corrected interval prolonged | Investigations | Systematic Assessment |
| ||
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Chest pain - cardiac | Cardiac disorders | Systematic Assessment |
| ||
| Floaters | Eye disorders | Systematic Assessment |
| ||
| Restlessness | Psychiatric disorders | Systematic Assessment |
| ||
| Pain of skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Eye irritation | Eye disorders | Systematic Assessment |
| ||
| Generalized edema | General disorders | Systematic Assessment |
| ||
| Chloride increased | Investigations | Systematic Assessment |
| ||
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| wrist swelling | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Amnesia | Nervous system disorders | Systematic Assessment |
| ||
| Stroke | Nervous system disorders | Systematic Assessment |
| ||
| Hiccups | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hoarseness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Laryngeal hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Purpura | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rana Mckay | University of California, San Diego | 858-822-5354 | cancerCTO@health.ucsd.edu |
| Mar 24, 2026 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: P10096_A19ConsentPhase1(Untracked) | Dec 5, 2025 | Mar 24, 2026 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: P10096_A19ConsentPhase2(Untracked) | Dec 5, 2025 | Mar 24, 2026 | ICF_002.pdf |
Not provided
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001706 | Biopsy |
| D013048 | Specimen Handling |
| D009682 | Magnetic Resonance Spectroscopy |
| C531550 | olaparib |
| C581106 | radium Ra 223 dichloride |
| ID | Term |
|---|---|
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 | Phase II Arm II (Radium Ra 223 Dichloride) | Patients receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study. Biopsy Procedure: Undergo tissue biopsy Biospecimen Collection: Undergo blood sample collection Computed Tomography: Undergo CT Laboratory Biomarker Analysis: Correlative studies Magnetic Resonance Imaging: Undergo MRI Quality-of-Life Assessment: Ancillary studies Radium Ra 223 Dichloride: Given IV |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|