Olaparib for Advanced Cancer

Not currently recruiting at 60 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Other malignancy, Brain metastases, 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: 1

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug olaparib treats certain advanced cancers. It focuses on patients with glioma, cholangiocarcinoma, or other solid tumors that have specific genetic mutations (IDH1 or IDH2) and have metastasized. The researchers aim to determine if olaparib can halt tumor growth when other treatments have failed. Suitable participants have confirmed IDH1 or IDH2 mutations and cancer that has spread. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for specific drugs. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before starting the trial. It's important to discuss your current medications with the trial team to ensure they don't interact with the study drug.

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

Research shows that olaparib is usually well-tolerated by patients with advanced cancer. Earlier studies identified common side effects such as nausea, tiredness, and anemia, which is a low red blood cell count. Most side effects were mild to moderate. Serious side effects occurred less frequently, though some patients did experience them.

The FDA has already approved olaparib for treating certain types of ovarian cancer, indicating a level of safety confidence. This approval means it has undergone thorough testing for safety and effectiveness in that context.

For those considering joining a trial with olaparib, it's important to know that side effects can vary. Discuss any concerns with a healthcare provider to understand how this treatment might affect you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olaparib is unique because it targets cancer cells with a specific mechanism of action known as PARP inhibition. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, olaparib specifically blocks the PARP enzyme, preventing cancer cells from repairing their DNA and leading to their death. This targeted approach can potentially lead to fewer side effects compared to conventional treatments. Researchers are excited about olaparib because it offers a new avenue for treating advanced cancers, especially those that have certain genetic mutations, like BRCA mutations, which make them more susceptible to this type of treatment.

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

Research has shown that olaparib, the treatment under study in this trial, can help treat some advanced cancers. In studies with ovarian cancer patients, olaparib significantly slowed disease progression. Patients who took olaparib with another drug, bevacizumab, had a 67% chance of their cancer not returning, compared to 30% for those who didn't take olaparib. This suggests that olaparib could be a promising option for controlling tumor growth. Although there is less data for brain tumors (glioma), bile duct cancer (cholangiocarcinoma), or tumors with IDH1 or IDH2 mutations, olaparib blocks enzymes that cancer cells need to grow, providing a strong rationale for its potential effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Patricia M Lorusso

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with advanced glioma, cholangiocarcinoma, or solid tumors that have IDH1/IDH2 mutations and are treatment-resistant can join. They must meet certain health criteria like blood cell counts, organ function tests, agree to use contraception if applicable, and be willing to undergo biopsies. Those with recent major surgery, uncontrolled medical issues, HIV/hepatitis or a history of other cancers may not qualify.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

Leukocytes >= 3,000/mcL

Platelet count >= 100 x 10^9/L

Exclusion Criteria

I haven't had chemotherapy or radiotherapy (except for comfort care) in the last 3 weeks.

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I do not have any serious, uncontrolled health issues or infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Monthly visits for CT/MRI scans, tumor biopsy, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The trial is testing Olaparib's effectiveness on patients whose cancer has spread and doesn't respond to standard treatments. It involves taking the drug orally and monitoring its impact through various assessments including biopsies and imaging techniques like CT scans and MRIs.

How Is the Trial Designed?

Group I: Treatment (olaparib) Experimental Treatment 5 Interventions

Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI, as well as a tumor biopsy and blood sample collection on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 (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, 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 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]

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, 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]

Citations

1. 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%.

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9870219/

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 two thirds of ...

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

LYNPARZA SOLO-1 Trial: Efficacy in Ovarian Cancer | For HCPs Read about the efficacy of LYNPARZA® (olaparib) as a 1L maintenance treatment for BRCAm advanced ovarian cancer in SOLO-1 study design.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1810858

Maintenance Olaparib in Patients with Newly Diagnosed ... The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ...

6. lynparzahcp.com lynparzahcp.com/ovarian-cancer/home.html

LYNPARZA PARP Inhibitor for Advanced Ovarian Cancer LYNPARZA® (olaparib) is a PARPi approved for first-line maintenance in BRCAm and HRD-positive advanced ovarian cancer.

7. lynparza.com lynparza.com/

LYNPARZA® (olaparib) - Official Patient Website Find out about LYNPARZA® (olaparib), a targeted treatment for certain types of cancer. See important safety information, downloadable resources and more.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9555119/

Tolerability of maintenance olaparib in newly diagnosed ... HIGHLIGHTS. Detailed safety data from the SOLO1 trial of maintenance olaparib in newly diagnosed, advanced BRCA-mutated ovarian cancer.

10. accc-cancer.org accc-cancer.org/docs/ossn-network/industry-news-announcements/solo3-dhcp.pdf?sfvrsn=b70b4ab8_2

solo3-dhcp.pdf Safety data, other than OS, reported for Lynparza in the SOLO3 study were consistent with those reported in other clinical trials with Lynparza. This letter is ...