Olaparib for Ovarian Cancer

Recruiting at 125 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

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

327 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)) who have responded following platinum based chemotherapy.

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.

What data supports the effectiveness of the drug Olaparib for ovarian cancer?

Olaparib has shown effectiveness in treating ovarian cancer, particularly in patients with BRCA mutations, by demonstrating antitumor activity and improving progression-free survival (the time during which the cancer does not get worse) in clinical trials. It is approved for use in patients with platinum-sensitive relapsed ovarian cancer, both with and without BRCA mutations, highlighting its potential benefit in maintaining cancer remission. ^{1 2 3 4 5}

Is Olaparib (Lynparza) safe for humans?

Olaparib (Lynparza) has been tested in various clinical trials for ovarian cancer and other conditions, showing it is generally safe for humans. However, like any medication, it can have side effects, and its safety profile includes monitoring for any unacceptable toxicity during treatment. ^{1 2 3 5 6}

How is the drug olaparib unique in treating ovarian cancer?

Olaparib is unique because it is an oral drug specifically designed for patients with BRCA mutation-positive ovarian cancer, working by inhibiting PARP enzymes that help repair DNA damage in cancer cells. This makes it a personalized treatment option, particularly effective for those with certain genetic profiles, and it is used as maintenance therapy after chemotherapy to prolong the period without disease progression. ^{1 2 4 5 7}

Research Team

Professor E Pujade-Lauraine, MD, PhD

Principal Investigator

Universite de Paris Descartes, France

Eligibility Criteria

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 am 18 years old or older.

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

I have a harmful BRCA1 or BRCA2 mutation.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. New Zealand pubmed.ncbi.nlm.nih.gov

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