Olaparib for Ovarian Cancer

Not currently recruiting at 156 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Platinum chemotherapy

Disqualifiers: Non detrimental BRCA mutations, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 28

Duration: 72 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests olaparib, a medication, to determine if it helps prevent the return of high-grade ovarian cancer in women with specific BRCA gene mutations. Participants will take either olaparib or a placebo (a pill with no active medicine) to compare effectiveness. Eligible women have had ovarian, primary peritoneal, or fallopian tube cancer that recurred after treatment and responded to platinum-based chemotherapy. The trial aims to determine if olaparib can delay cancer recurrence longer than a placebo. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that maintenance treatment is allowed at the end of the penultimate platinum regimen, which might suggest some flexibility. It's best to discuss your specific medications with the trial team.

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

Research has shown that olaparib has been tested for safety in many studies. The OPINION trial found that olaparib's safety matched previous results, with no new safety issues. In another study, SOLO-1, olaparib was generally well-tolerated, though some participants experienced side effects like nausea, tiredness, and low red blood cell count, which are common with many cancer treatments.

Further research with 181 patients in Japan supported these findings, indicating that olaparib's safety is well-understood. While some side effects might occur, they are usually manageable and expected with this type of medication. ^{1 2 3 4 5}

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

Researchers are excited about Olaparib for ovarian cancer because it offers a novel approach by targeting the cancer cells' ability to repair DNA. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Olaparib specifically inhibits the PARP enzyme, preventing cancer cells from fixing their DNA and leading to cell death. This targeted mechanism not only promises to be more effective but also potentially reduces side effects compared to conventional treatments.

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

Research has shown that olaparib, which participants in this trial may receive, effectively treats ovarian cancer, particularly in patients with certain BRCA mutations. One study found that the time patients lived without their cancer worsening was not reached with olaparib, indicating a strong benefit compared to 13.8 months with a placebo. Additionally, 67% of patients taking olaparib with bevacizumab did not experience cancer growth, compared to 30% of those taking bevacizumab with a placebo. Long-term data also indicate that olaparib can significantly extend overall survival. These findings suggest that olaparib is a promising treatment option for ovarian cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Professor E Pujade-Lauraine, MD, PhD

Principal Investigator

Universite de Paris Descartes, France

Are You a Good Fit for This Trial?

This trial is for women over 18 with high-grade serous ovarian cancer or endometrioid cancer, who have a harmful BRCA mutation. They should have had at least two platinum-based chemotherapies and be in partial or complete response to the last one without CA-125 increase. They can't join if they've been involved in study planning/conduct or have non-detrimental BRCA mutations.

Inclusion Criteria

I have had at least 2 treatments with platinum-based drugs before.

I have a harmful BRCA1 or BRCA2 mutation.

I finished my chemotherapy less than 8 weeks ago.

Exclusion Criteria

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

I had fluid drained from my abdomen during my last two chemotherapy cycles.

My BRCA1 or BRCA2 mutation is not considered harmful.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib or placebo tablets orally twice daily

72 weeks

Radiologic scans at baseline then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 36 months

Assessments every 12 weeks until second progression

Long-term follow-up

Participants are assessed for overall survival and quality of life

up to 75 months

Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The study tests Olaparib tablets (300mg) against a placebo in patients with certain types of ovarian cancer who responded to previous chemotherapy. It's a Phase III trial where participants are randomly assigned to either the drug or placebo, and neither they nor the doctors know which one they're getting.

How Is the Trial Designed?

Group I: Olaparib 300mg tablets Experimental Treatment 1 Intervention

Taken orally twice daily

Group II: Placebo tablets Placebo Group 1 Intervention

Taken orally twice daily

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Myriad Genetic Laboratories, Inc.

Industry Sponsor

Trials

32

Recruited

14,600+

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 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 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 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]

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]

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]

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]

Citations

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

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

2. 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%.

3. 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 ...

4. 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 ...

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40300425/

Final overall survival results from the OPINION trial The safety profile was consistent with the primary analysis and known safety profile of olaparib, with no new safety findings. Keywords: BRCA; Maintenance; ...

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 ...