Olaparib for Advanced Cancer

Not currently recruiting at 179 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Colony-stimulating factors, PARP inhibitors

Disqualifiers: Active malignancy, CNS metastases, HIV, 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: Unknown

Duration: Up to 53 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests olaparib, a medication, to evaluate its effectiveness and safety for individuals with advanced cancer that has spread or cannot be surgically removed. The study targets cancers unresponsive to other treatments and with specific genetic changes related to DNA repair. Participants may qualify if they have advanced cancer with these genetic features and have not succeeded with standard treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received any anti-cancer treatments like chemotherapy, biological therapy, or targeted therapy within 3 weeks before starting the study. It's best to discuss your current medications with the study team.

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

Research has shown that olaparib has undergone testing in several studies for safety. One study used olaparib alone to treat patients with advanced ovarian cancer and found it effective against tumors.

Regarding safety, another study found that most patients managed olaparib's side effects well. However, as with any treatment, some patients experienced unwanted effects, which can vary from person to person.

Overall, different studies have used olaparib, and many patients have tolerated it well. Discussing potential risks and benefits with a healthcare provider is always advisable before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olaparib is unique because it specifically targets cancer cells with certain genetic mutations, known as homologous recombination repair mutations (HRRm) or homologous recombination deficiency (HRD)-positive cancers. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, olaparib works as a PARP inhibitor, blocking a protein that cancer cells need to repair their DNA, leading to their death. This targeted approach not only increases effectiveness but also potentially reduces the side effects often seen with more generalized treatments. Researchers are excited because this could mean a more personalized and less toxic treatment option for patients with advanced cancer.

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

Research has shown that olaparib, which participants in this trial will receive, effectively treats certain advanced cancers, particularly those with specific genetic traits like HRRm or HRD. In one study, 67% of patients with advanced ovarian cancer experienced no cancer growth or return when treated with olaparib and another drug, compared to only 30% who received the other drug alone. Long-term research suggests that olaparib can help patients live longer when included in cancer treatment. It is the first treatment of its kind shown to extend life in early breast cancer studies. Overall, these findings support olaparib as a promising treatment for cancers with the right genetic background. ^{3 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced cancers that have worsened after standard care or if they're intolerant to it. They must have specific genetic changes (HRRm/HRD positive) and be able to provide a biopsy. Participants need a life expectancy of at least 3 months, good organ function, and an ECOG status of 0 or 1. Men must use contraception; women not pregnant/breastfeeding should also use effective birth control.

Inclusion Criteria

My advanced cancer has no cure and standard treatments have failed.

My breast cancer is due to a BRCA mutation.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have been diagnosed with MDS, AML, or conditions that suggest I might have them.

You are allergic to the ingredients in olaparib.

I have an active hepatitis infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral olaparib, 300 mg twice daily (BID) for advanced cancer treatment

Up to 53 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview

The study tests Olaparib's effectiveness and safety in treating various advanced cancers with certain genetic mutations (HRRm/HRD). Patients previously treated without success are given this medication as monotherapy to see how well it works against their cancer.

How Is the Trial Designed?

Group I: Olaparib Experimental Treatment 1 Intervention

Participants with HRRm or HRD-positive advanced cancer will receive oral olaparib, 300 mg twice daily (BID).

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?

Merck Sharp & Dohme LLC

Lead 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

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

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 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]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., 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 (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 oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[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, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

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.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12342895/

Treatment, outcomes, and resource utilization among patients ...

We investigated clinical characteristics, treatment, clinical outcomes, and health-care resource utilization by BRCA1/2 or HRD status among ...

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.

esmoopen.com

esmoopen.com/article/S2059-7029(24)01754-X/pdf

Long-term outcomes of PARP inhibitors in ovarian cancer

In conclusion, long-term survival data further support the use of PARPi as maintenance strategy after PBC in the first line, where OS benefit ...

4.

astrazeneca-us.com

astrazeneca-us.com/media/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

LYNPARZA® (olaparib) demonstrated clinically meaningful ...

87.5% of patients treated with LYNPARZA were alive at six years vs. 83.2% in the comparator arm. First and only PARP inhibitor to improve ...

5.

lynparzahcp.com

lynparzahcp.com/ovarian-cancer/testing/hrd-testing.html

Ovarian Cancer HRD Testing

In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who ...

6.

pmc.ncbi.nlm.nih.gov

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

Efficacy and safety of olaparib monotherapy in germline ...

olaparib 400 mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer.

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.22.01549

Overall Survival With Maintenance Olaparib at a 7-Year ...

Indeed, the SOLO1 OS data support the use of maintenance olaparib to achieve long-term remission in BRCA-mutated patients with newly diagnosed ...

8.

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 ...

9.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1810858

Maintenance Olaparib in Patients with Newly Diagnosed ...

The safety profile of olaparib appeared to be generally acceptable in patients receiving maintenance treatment for newly diagnosed advanced ...