Experimental Combination of Olaparib and Radium-223 For Metastatic Castration-Resistant Prostate Cancer That Has Spread

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Age: 18 years or older
Gender:
Male
Healthy Volunteers: No
Keywords: prostate cancer, Metastatic Castration-Resistant Prostate Cancer, Castration-Resistant Prostate Cancer, Metastatic Castration-Resistant Prostate Cancer with Bone Metastases, Cancer with Bone Metastases
Type: Other study, Phase [/1/,/ /2/]
Target:
120 Participants
Investigator:
Description
This study is for patients with metastatic castration resistant prostate cancer. In this study, we hope to learn if we can lower the chance of your prostate cancer growing or spreading. We will test the addition of the experimental drug, olaparib, to usual treatment with radium-223.

We are doing this study because we want to find out if this approach is better or worse than the usual approach. The usual approach is defined as care most people get for metastatic castration resistant prostate cancer.

The usual approach for patients who are not in a study is treatment with chemotherapy or hormone therapy. Sometimes, combinations of these treatments are used. Additional available options include radiation therapy for some individuals. Your doctor can explain which treatment may be best for you. These treatments can reduce symptoms and may stop the tumor from growing for a few months or longer.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  • 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 agonist/antagonist; participants receiving prior docetaxel or abiraterone for hormone sensitive disease are permitted
  • Participants must have progressive disease as defined by the following:
  • Castrate resistant disease as defined by PCWG-3 criteria; participants must have a rise in PSA on two successive determination at least one week apart and PSA levels >= 2 ng/mL (only the screening PS needs to be >= 2 ng/mL) and serum testosterone < 50 ng/dL
  • Soft tissue progression as defined by RECIST version 1.1
  • Bone disease progression as defined by PCWG-3 criteria including the development of two or more new lesions on bone scan
  • 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
  • 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 prior to administration of study treatment)
  • Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 prior to administration of study treatment)
  • Platelets >= 100,000/mcL (within 28 prior to administration of study treatment)
  • Hemoglobin >= 10 g/dL (transfusions permitted) (within 28 prior to administration of study treatment)
  • Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN) (within 28 prior to administration of study treatment)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 prior to administration of study treatment)
  • Creatinine clearance >= 51 ml/min as defined by Cockcroft-Gault equation (within 28 prior to administration of study treatment)
  • 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
  • Persistent grade > 1 CTCAE version 5.0 adverse events (except alopecia)
  • 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 cytotoxic chemotherapy, hormonal therapies (including but not limited to abiraterone, enzalutamide), investigational prostate cancer directed therapy 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:
  • Cerebral infarction within 6 months of study treatment
  • Transient ischemic attack within 3 months of study treatment
  • Myocardial infarction within 6 months of study treatment
  • Uncontrolled angina within 3 months of study treatment
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multiā€gated acquisition scan performed within 3 months of the screening visit results in a left ventricular ejection fraction that is >= 45%
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
  • Prolonged corrected QT interval by the Fridericia correction formula on the screening electrocardiogram (ECG) > 470 msec
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
  • Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
  • History of hypertensive emergency or encephalopathy within 6 months of study treatment
  • Deep venous thrombosis or pulmonary embolism within 3 months of study treatment
  • 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 5 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:
  • Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or
  • Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: superficial bladder cancer, basal cell or squamous cell carcinoma of the skin
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
You will receive study treatment every 28-days for up to 6 doses. After study treatment ends, the doctor may follow-up with you for up to 2 years (phone or medical record review).
Recruitment period
From Jan. 8, 2019
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Research Topic
Conditions:
  • Castration-Resistant Prostate Carcinoma
  • Prostate Adenocarcinoma
  • Prostate Carcinoma Metastatic in the Bone
  • Testosterone Less Than 50 ng/dL

Have any questions or want to learn more? Leave your contact details below and the research team will reach out to you.


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