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

Trial Summary

What is the purpose of this trial?

This is a prospective non-randomized efficacy trial of olaparib maintenance therapy after frontline treatment with platinum-based therapy in advanced ovarian cancer patients with BRCAwt, homologous recombination deficient (HRD) disease.

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.

What data supports the idea that Olaparib for Ovarian Cancer is an effective drug?

The available research shows that Olaparib is effective for treating ovarian cancer, especially in patients with certain genetic mutations. Studies have shown that Olaparib helps women with relapsed ovarian cancer who have a BRCA1 or BRCA2 mutation, which are changes in genes that can lead to cancer. It is used as a maintenance therapy, meaning it helps keep the cancer from coming back after initial treatment. Olaparib has been approved for use in Europe and the USA for patients with these mutations. Additionally, it is being tested in patients without these mutations, showing promise in those with other types of genetic issues related to DNA repair. This suggests that Olaparib could be beneficial for a broader group of patients. ^{1 2 3 4 5}

What safety data is available for Olaparib in treating ovarian cancer?

Olaparib (Lynparza) has been evaluated for safety in multiple studies. It is approved for use in patients with BRCA mutation-positive ovarian cancer, particularly for platinum-sensitive recurrent disease. Safety data from trials indicate it is used as maintenance therapy following platinum-based chemotherapy. The OPINION Phase IIIb study is assessing its safety in patients without germline BRCA mutations. Olaparib has been tested in Phase I, II, and III trials, showing promising activity and safety in both germline BRCA mutated and sporadic ovarian cancer. ^{1 2 3 4 6}

Is the drug Olaparib a promising treatment for ovarian cancer?

Yes, Olaparib is a promising drug for treating ovarian cancer, especially in patients with BRCA mutations. It has shown significant antitumor activity and can improve progression-free survival in these patients. It is approved for use in certain cases of ovarian cancer and is generally well tolerated. ^{1 2 3 5 7}

Research Team

Alexander B. Olawaiye

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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 (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

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

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

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

4. 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]

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

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

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]