Olaparib for Prostate Cancer

Not currently recruiting at 2 trial locations

Overseen By Catherine H Marshall, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Anti-androgens, Chemotherapy, PARP inhibitors, others

Disqualifiers: HIV, Hepatitis B/C, MDS/AML, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Minimum 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of olaparib (also known as Lynparza, a type of targeted cancer therapy) for treating prostate cancer, specifically in cases where the cancer has not spread. The study focuses on patients with prostate cancer who have specific genetic mutations affecting DNA repair. Researchers aim to determine if taking olaparib earlier in the disease process is effective, rather than waiting until the cancer advances. Participants should have undergone prostate surgery, possibly radiation, and show no signs of cancer spreading on recent scans. The trial is for those who haven't recently used certain hormone therapies and can take oral medication. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in prostate cancer therapy.

Do I need to stop my current medications to join the trial?

You may need to stop taking certain medications before joining the trial. Specifically, if you are using strong or moderate CYP3A inhibitors or inducers, you will need to stop them for a washout period of 2 to 5 weeks, depending on the medication, before starting olaparib.

Is there any evidence suggesting that olaparib is likely to be safe for humans?

Research shows that olaparib is generally safe for patients with advanced prostate cancer that no longer responds to hormone therapy. Studies have found that patients using olaparib often experience manageable side effects. For example, one study found that 85% of patients did not have increased pain after six months of treatment, suggesting the treatment is manageable.

However, like most medications, olaparib can cause side effects. These may include tiredness, nausea, and low levels of red blood cells (anemia). It's important to remember that these side effects can vary for each person.

Overall, current research indicates that the safety of olaparib is promising. Consulting a healthcare provider is advisable to understand what to expect and to ensure it is the right choice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Olaparib is unique because it belongs to a class of drugs called PARP inhibitors, which work by targeting and blocking a protein that cancer cells need to repair DNA damage. Unlike traditional treatments for prostate cancer, such as hormone therapy or chemotherapy, olaparib specifically exploits the weakness in cancer cells with DNA repair defects, like those with BRCA mutations. This targeted approach not only has the potential to be more effective in these specific genetic contexts but may also offer a better side effect profile, making it an exciting option for researchers and patients alike.

What evidence suggests that olaparib might be an effective treatment for prostate cancer?

Research has shown that olaparib, the treatment under study in this trial, may effectively treat advanced prostate cancer, especially in patients with certain genetic mutations. In one study with 49 patients, 11 experienced a significant decrease in PSA levels, a marker used to monitor prostate cancer. Patients who showed improvement on scans also had lower PSA levels, indicating the drug's effectiveness. Another study found that patients taking olaparib lived longer, with an average survival of 19.1 months compared to 14.7 months for those on other treatments. Additionally, 85% of patients on olaparib did not experience increased pain after six months, compared to 75% in the control group. Overall, olaparib has shown significant benefits in treating prostate cancer, particularly for those with specific genetic profiles. ^{1 2 3 5 6}

Who Is on the Research Team?

Catherine H Marshall, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Men with high-risk, non-metastatic prostate cancer post-prostatectomy can join this trial. They should have a rapidly rising PSA level, good physical condition (ECOG 0-1), and no prior ADT or strong CYP3A inhibitors in the last 6 months. Participants need normal organ/bone marrow function and agree to use effective contraception.

Inclusion Criteria

My recent scans show no signs of cancer spread.

PSADT ≤6 months, based upon ≥3 consecutive measurements collected in the past 12 months, at least 4 weeks apart

My organ and bone marrow functions are normal as tested within the last 28 days.

Exclusion Criteria

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I had major surgery more than 2 weeks ago and have recovered from it.

I cannot swallow pills or have a stomach condition that affects medication absorption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib at 300mg twice daily until PSA doubling, development of metastatic disease, or unacceptable toxicity

Minimum 12 weeks

Monthly clinic visits for safety labs, PSA, and toxicity assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for PSA progression-free survival and treatment-related adverse events

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The trial is testing Olaparib's effectiveness for prostate cancer at an earlier stage than previously studied. It involves men whose cancer has returned biochemically after surgery but hasn't spread elsewhere, focusing on those with specific genetic mutations linked to DNA repair.

How Is the Trial Designed?

Group I: Olaparib 300 mg BID Experimental Treatment 1 Intervention

Patients will be administered olaparib orally twice daily at 300mg bid continually. Two 150mg of olaparib tablets should be taken twice daily, approximately 12 hours apart with one glass of water.

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

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. 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 ...

3. 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.

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

LYNPARZA PROfound Trial for HRRm mCRPC | Efficacy Data ... 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).

5. sciencedirect.com sciencedirect.com/science/article/pii/S2352396424003244

Articles Assessing olaparib efficacy in US Veterans with ... Olaparib is an effective medication in patients with prostate cancers harboring diverse HRR alterations, albeit slowing of tumor growth with prolongation of ...

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

Research Shows Promising Outcomes for Prostate Cancer ... This trial revealed that patients receiving olaparib monotherapy had longer treatment duration, improved progression-free survival, and improved ...