Olaparib for Ovarian Cancer

Overseen By Joshua Plassmeyer, MS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Alexander B Olawaiye, MD

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: BRCA mutation, Cardiovascular disease, Pregnancy, 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: 12

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of olaparib as a follow-up treatment for advanced ovarian cancer with a specific genetic profile (BRCAwt, homologous recombination deficient). Patients take olaparib as a pill twice daily, which could help prevent cancer recurrence after initial treatment. The study seeks participants diagnosed with advanced ovarian cancer who lack a BRCA mutation but whose cancer cells show signs of repair difficulty. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot use strong or moderate CYP3A4 inhibitors or inducers. If you are taking these, you need a washout period of 2 weeks for inhibitors and 3-5 weeks for inducers before starting the trial.

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

Research shows that olaparib is generally safe for patients. Safety data from earlier studies, such as the SOLO-1 trial, indicate that while some people may experience side effects, these are usually manageable. Common side effects include nausea and fatigue. A Japanese study with 181 ovarian cancer patients confirmed olaparib's consistent safety record, revealing no new safety issues. These findings support olaparib's known and reliable safety profile for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olaparib is unique because it targets ovarian cancer by inhibiting a protein called PARP, which plays a key role in DNA repair. Unlike traditional chemotherapy, which attacks rapidly dividing cells broadly, Olaparib specifically cripples cancer cells that are already weakened by their inability to repair DNA. This precision makes it especially promising for patients with BRCA mutations, offering a more tailored approach. Researchers are excited because it may enhance treatment effectiveness while potentially reducing side effects compared to standard chemotherapy.

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

Research has shown that olaparib effectively treats ovarian cancer. In one study, 67% of patients who took olaparib with bevacizumab did not experience cancer growth or recurrence, compared to 30% of those on a placebo. Another study found that patients on olaparib had a longer time before their cancer worsened or returned. Additionally, a review of several studies found that olaparib can significantly extend the lives of ovarian cancer patients. In this trial, participants will receive olaparib as a maintenance treatment, which could serve as a valuable ongoing option for advanced ovarian cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Alexander B. Olawaiye

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for advanced ovarian cancer patients with BRCAwt and homologous recombination deficiency. Participants must have a good performance status, life expectancy over 16 months, normal organ/marrow function, measurable disease per RECIST 1.1 criteria, and no prior enrollment in this study or recent investigational drug use.

Inclusion Criteria

You have a disease that can be measured using a specific set of guidelines.

You are expected to live for at least 16 months.

My blood and organ functions are within normal ranges.

Exclusion Criteria

You have had a heart attack or unstable chest pain within the last 6 months, have severe heart failure, or other significant heart problems. You also have a history of certain types of strokes or bleeding disorders, or have signs of brain or spinal cord problems. Additionally, you have other health issues or conditions that could make it risky for you to take the study drug.

Your recent heart test shows serious problems that are not being treated, or you have a certain heart condition called congenital long QT syndrome.

I have been taking more than 325 mg of aspirin daily for the last 10 days or longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance olaparib monotherapy after frontline treatment with platinum-based therapy

12 months

Every 12 weeks during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The trial tests the effectiveness of olaparib tablets as maintenance therapy following initial platinum-based treatment in these specific ovarian cancer patients. It's a prospective non-randomized study focusing on those without BRCA mutations but with homologous recombination deficiencies.

How Is the Trial Designed?

Group I: Olaparib (maintenance) Experimental Treatment 1 Intervention

300 mg Olaparib (tablets) will be taken orally, twice a day (approximately every twelve hours)

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?

Alexander B Olawaiye, MD

Lead Sponsor

Trials

4

Recruited

130+

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

Published Research Related to This Trial

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Citations

1. lynparza.com lynparza.com/ovarian-cancer/results/advanced-ovarian-cancer.html

Results of LYNPARZA: advanced ovarian cancer 168 out of 255 patients on LYNPARZA + bevacizumab did not see their cancer grow or return compared with 40 out of 132 patients on bevacizumab + placebo. 67%.

2. lynparzahcp.com lynparzahcp.com/ovarian-cancer/efficacy/solo-1.html

LYNPARZA SOLO-1 Trial: Efficacy in Ovarian Cancer | For HCPs Primary analysis. Unprecedented efficacy: Median PFS was not reached with LYNPARZA vs ~1.2 years (13.8 months) with placebo1,5.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8921481/

Systematic Review of Olaparib in the Treatment ... The results showed that HR = 1.24 (95%CI = 1.06-1.45, P = 0.006), suggesting that Olaparib can significantly prolong OS in patients with ovarian cancer, as ...

4. onclive.com onclive.com/view/olaparib-withstands-the-test-of-time-with-long-term-data-supporting-its-role-in-ovarian-cancer-treatment

Olaparib Withstands the Test of Time With Long-Term Data ... The primary outcome was progression-free survival [PFS], and for women randomized to olaparib, the chances of progression or death were reduced ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01549

Overall Survival With Maintenance Olaparib at a 7-Year ... Results indicate a clinically meaningful, albeit not statistically significant, improvement in OS with maintenance olaparib versus placebo, with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4992984/

Efficacy and safety of olaparib monotherapy in germline ... With olaparib monotherapy, objective tumor response rates in Study 42 were 26% for all patients with gBRCA1/2m cancers, and 31% for patients with gBRCA1/2m ...

7. lynparzahcp.com lynparzahcp.com/ovarian-cancer/safety-tolerability/solo-1.html

Safety & Tolerability in the SOLO-1 Trial Learn about the safety profile and tolerability of LYNPARZA® (olaparib) as well as the potential adverse reactions found in the SOLO-1 ...

8. nature.com nature.com/articles/s41598-024-63600-z

Safety assessments and clinical features of PARP ... This retrospective study included 181 patients with ovarian cancer who received olaparib or niraparib at two independent hospitals in Japan between May 2018 ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0090825825008066

Final overall survival results from the OPINION trial The updated safety data remained consistent with the primary analysis and the known safety profile of olaparib, with no new safety findings, building on ...