Olaparib Maintenance Therapy for Ovarian Cancer

(SOLO-1 Trial)

Recruiting at 176 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Platinum chemotherapy

Disqualifiers: Early stage, Stable disease, 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: 36

Duration: Up to 156 weeks

450 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Olaparib (Lynparza) has shown effectiveness as a maintenance therapy for women with relapsed ovarian cancer, particularly those with BRCA mutations, by prolonging the time before the cancer progresses. It is approved for use in patients who have responded to previous platinum-based chemotherapy, demonstrating its ability to help maintain remission. ^{1 2 3 4 5}

Is Olaparib (Lynparza) safe for use in humans?

Olaparib (Lynparza) has been tested in various clinical trials and is generally considered to have a manageable safety profile. It is used for maintenance therapy in ovarian cancer and has been approved for use in patients with certain genetic mutations, showing that it is generally safe for human use. ^{1 2 3 4 6}

How is the drug olaparib unique in treating ovarian cancer?

Olaparib is unique because it is a PARP inhibitor (a type of drug that blocks an enzyme involved in repairing damaged DNA) used as a maintenance therapy for ovarian cancer, particularly in patients who have responded to platinum-based chemotherapy, even if they do not have BRCA mutations. This makes it different from other treatments that typically target BRCA mutation-positive patients. ^{1 2 3 4 7}

What is the purpose of this trial?

Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

Research Team

Kathleen Moore, M.D., MS

Principal Investigator

University of Oklahoma Health Sciences Center, Oklahoma City, USA

Prof Paul DiSilvestro, MD

Principal Investigator

Women & Infants Hospital, Providence, Rhode Island, USA

Eligibility Criteria

This trial is for women with newly diagnosed high-grade ovarian cancer (FIGO stage III-IV) that have specific harmful mutations in BRCA genes. They should have responded well to first-line platinum-based chemotherapy and undergone debulking surgery if needed. Women with stable or worsening disease post-chemotherapy, early-stage cancer, multiple surgeries before the study, or previous chemo for abdominal tumors are excluded.

Inclusion Criteria

I've had surgery aimed at removing as much cancer as possible.

I have a harmful BRCA1 or BRCA2 mutation.

I am a woman with advanced ovarian, peritoneal, or fallopian tube cancer with a BRCA mutation and have finished first-line platinum chemotherapy.

Exclusion Criteria

I have early-stage endometrial cancer and am under 60, or I'm 60+ with a specific early cancer type.

My BRCA1/2 mutations are not harmful.

My cancer did not improve but also did not worsen after my first chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Olaparib or placebo tablets p.o. 300mg twice daily for up to 3 years or until disease progression

Up to 156 weeks

Visits every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Visits every 24 weeks

Open-label extension (optional)

Participants may continue treatment beyond 2 years if in their best interest

Long-term

Treatment Details

Interventions

• Olaparib

Trial Overview The trial tests Olaparib tablets as a maintenance therapy for patients who've had a positive response to initial chemotherapy. It's aimed at preventing cancer from coming back by targeting BRCA mutations which are common in high-grade ovarian cancers.

Participant Groups

Group I: Olaparib tablets p.o. 300mg twice daily Experimental Treatment 1 Intervention

Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity

Group II: Placebo tablets p.o. twice daily Placebo Group 1 Intervention

Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity

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

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

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

Myriad Genetic Laboratories, Inc.

Industry Sponsor

Trials

32

Recruited

14,600+

Findings from Research

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, 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 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 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]

In a study of 115 relapsing epithelial ovarian cancer patients with BRCA mutations receiving olaparib, the median progression-free survival (PFS) was 12.7 months and overall survival (OS) was 35.4 months after a median follow-up of 21 months.

Key factors associated with longer PFS and OS included a platinum-free interval of 12 months or more, achieving a complete or partial response to treatment, and normalization of CA-125 levels after the last platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers. Labidi-Galy, SI., de La Motte Rouge, T., Derbel, O., et al.[2022]

Olaparib is an effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[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]

References

1. 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]

2. 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]

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

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

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

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

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

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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