Olaparib + Radium-223 for Prostate Cancer

Recruiting at 23 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: LHRH agonist/antagonist, Bisphosphonates, Denosumab

Must not be taking: CYP3A4/5 inducers/inhibitors

Disqualifiers: Small cell carcinoma, Visceral metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 19

133 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Rana McKay, MD

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

Men with advanced prostate cancer that has spread to the bones and is resistant to castration can join this trial. They must have low testosterone levels, progressive disease, at least two bone metastases not previously treated with radiation, and be able to take oral medications. Men must agree to use contraception and avoid sperm donation during the study. Those with HIV are eligible if well-controlled.

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 (LHRH) agonist/antagonist; participants receiving prior docetaxel abiraterone, or next generation AR antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease are permitted

Exclusion Criteria

Patient unable to swallow orally administered medication

Deep venous thrombosis or pulmonary embolism within 3 months of study treatment

Prior treatment with radium-223

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase I Treatment

Patients receive radium Ra 223 dichloride IV and olaparib PO BID. Treatment repeats every 28 days for up to 6 cycles.

24 weeks

6 visits (in-person)

Phase II Treatment

Patients are randomized to receive radium Ra 223 dichloride and olaparib, with potential crossover for progression.

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2 years

Every 6 months

Treatment Details

Interventions

• Olaparib
• Radium Ra 223 Dichloride

Trial Overview The trial is testing different doses of Olaparib combined with Radium-223 in men whose prostate cancer has spread to their bones. Olaparib blocks proteins that repair tumor DNA, potentially stopping cancer growth; Radium-223 delivers radiation directly to tumor cells.

Participant Groups

Group I: Arm II (radium Ra 223 dichloride) Experimental Treatment 7 Interventions

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.

Group II: Arm I (radium Ra 223 dichloride, olaparib) Experimental Treatment 8 Interventions

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.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+