Olaparib + Radium-223 for Prostate Cancer

Not currently recruiting at 26 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment combination for men with prostate cancer that has spread to bones and no longer responds to hormone therapy. It combines olaparib (Lynparza), a drug that prevents cancer cells from repairing themselves, with radium-223, a radioactive drug targeting cancer cells in bones. The trial aims to determine the best dose, understand side effects, and evaluate the combination's effectiveness. Men with prostate cancer that has spread to at least two bone sites and continues to progress despite hormone therapy may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination therapy.

Do I have to stop taking my current medications for the trial?

The trial requires stopping certain medications before starting the study. Specifically, you must stop taking enzalutamide, phenobarbital, and other CYP3A inducers 3-4 weeks before starting olaparib. If you're on strong CYP3A inhibitors, a 2-week washout period is needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining olaparib with radium Ra 223 dichloride is generally safe for patients. Studies have found that these treatments can be combined without major safety issues, and some patients have experienced early benefits.

Since 2013, radium Ra 223 has been used to treat prostate cancer. It often helps patients live longer and is usually well-tolerated. Patients who complete most of their treatment cycles tend to achieve better results.

Overall, studies have shown that both olaparib and radium Ra 223 are fairly safe. This is encouraging for those considering participation in a trial with these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine innovative approaches that target cancer more precisely. Olaparib works by inhibiting PARP enzymes, which play a crucial role in repairing DNA damage in cancer cells, potentially leading to their death. Radium-223 dichloride, on the other hand, is a radiopharmaceutical that specifically targets bone metastases, delivering radiation directly to cancerous areas in the bone. This dual approach not only targets the cancer more effectively but also minimizes damage to healthy tissue, offering hope for improved outcomes compared to traditional treatments like hormone therapy and chemotherapy.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that olaparib, a PARP inhibitor, effectively treats advanced prostate cancer that no longer responds to hormone therapy. It extends patient survival to an average of 19.1 months, compared to 14.7 months with other treatments. Additionally, 85% of patients taking olaparib did not experience worsening pain after 6 months. In this trial, some participants will receive olaparib combined with radium Ra 223 dichloride.

Radium Ra 223 dichloride targets cancer that has spread to the bones in prostate cancer patients. Studies indicate it can extend life and delay bone-related symptoms. On average, patients treated with radium-223 live for 15.7 months. In this trial, some participants will receive radium Ra 223 dichloride alone, with the option to add olaparib if radiographic progression occurs. Both treatments have shown promise individually, so combining them might enhance their effectiveness against prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Rana McKay, MD

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. lynparza.com lynparza.com/prostate-cancer/results.html

Metastatic Prostate Cancer Treatment Results The median time of survival after the start of LYNPARZA was 19.1 months vs 14.7 months on enzalutamide or abiraterone. FOR ADULTS WITH BRCA1, BRCA2, OR ATM ...

2. dukecancerinstitute.org dukecancerinstitute.org/blogs/research-shows-promising-outcomes-prostate-cancer-patients-treated-olaparib

Research Shows Promising Outcomes for Prostate Cancer ... Olaparib, a targeted therapy used to treat prostate cancer, showed significant benefits in patients with homologous recombination repair (HRR) gene mutations.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1911440

Olaparib for Metastatic Castration-Resistant Prostate Cancer After 6 months, 85% of the patients in the olaparib group were free of pain progression, as compared with 75% in the control group (Figure 3B). The median ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9520412/

Olaparib outcomes in metastatic castration-resistant prostate ... Olaparib is a highly effective oral PARP that has been approved for the treatment of prostate and other cancer10, 11, 12, 13.

5. lynparzahcp.com lynparzahcp.com/prostate-cancer/efficacy/monotherapy.html

LYNPARZA PROfound Trial for HRRm mCRPC Median OS with LYNPARZA was 19.1 months (95% CI: 17.4–23.4) vs 14.7 months with investigator's choice of enza or abi/pred (95% CI: 11.9–18.8).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10769512/

A Phase I Study of Combination Olaparib and Radium-223 ... Olaparib can be safely combined with radium-223 at the RP2D 200 mg orally twice daily with fixed dose radium-223. Early clinical benefit was observed and will ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-01920

Testing the Safety of Different Doses of Olaparib Given ... 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 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2588931125001725

Radium-223 in Men with Metastatic Castration-resistant ... Completion of five or more cycles of Ra-223 was associated with a two- to five-fold increase in overall survival. Ra-223 was well tolerated, with a safety ...

9. nature.com nature.com/articles/s41391-025-00969-6

Real-world utilization patterns and survival in men with ... Overall, median rwOS was 22.9 months. Median rwOS was longer in men who completed ≥5 Ra-223 cycles versus 1–4 cycles (30.3 versus 15.3 months) ...

10. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1385466/full

Outcomes and patterns of use of Radium-223 in metastatic ... Those patients who received 6 cycles of Ra-223 reached a better OS, a median of 19.26 months (95% CI, 14.43–21.45) compared to those who ...