Olaparib for Mesothelioma

Overseen By Hedy L Kindler, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Platinum agents

Must not be taking: PARP inhibitors, CYP3A inhibitors, CYP3A inducers

Disqualifiers: Uncontrolled illness, Other malignancy, Platinum-resistant, Cardiac conditions, 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 2 years

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called olaparib (also known as Lynparza) to determine if it can shrink or halt tumor growth in people with mesothelioma, a cancer often linked to asbestos exposure. Participants must have specific DNA changes (gene mutations) and should have previously received certain chemotherapy drugs. The trial aims to assess olaparib's effectiveness for those whose cancer responded well to platinum-based treatments in the past. Participants visit the clinic regularly to monitor progress and receive the drug in cycles. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting olaparib. Specifically, if you are using strong or moderate CYP3A inhibitors or inducers, you must stop them 2 to 5 weeks before starting the study drug, depending on the specific medication.

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

Research has shown that olaparib is generally safe for patients. Studies have not found any new safety issues with its use. Although olaparib lacks specific approval for mesothelioma, it has been administered to individuals with this condition. Its approval for other conditions supports its safety profile.

Olaparib is under investigation because some mesothelioma patients have specific gene changes that might respond well to it. Previous trials demonstrated that the drug is well-tolerated, with no unexpected side effects. This suggests that olaparib could be safe for mesothelioma patients with these gene changes. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for mesothelioma focus on chemotherapy, surgery, and radiation. However, Olaparib is unique because it targets the cancer at a genetic level. It works as a PARP inhibitor, which means it interferes with the cancer cell's ability to repair its DNA, leading to cell death. Researchers are excited about Olaparib because it offers a more targeted approach, potentially leading to better outcomes with fewer side effects compared to traditional therapies. This novel mechanism of action could represent a significant advance in the treatment of mesothelioma.

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

Research has shown that olaparib, the treatment under study in this trial, has limited success in treating mesothelioma. In studies, only 4% of patients responded to the treatment. On average, patients lived 3.6 months without their cancer worsening. Although olaparib is approved for some other cancers, its ability to shrink or stop mesothelioma tumors remains modest. Even patients with certain gene changes, such as BAP1 mutations, do not experience improved effectiveness with this drug. ^{1 2 6 7 8}

Who Is on the Research Team?

Hedy Kindler, M.D.

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for mesothelioma patients with specific DNA changes, who've had platinum-based chemo. They must be able to perform daily activities (ECOG 0-1), not have other active cancers, and agree to genetic testing. Women can't be pregnant, and men must use condoms during the study.

Inclusion Criteria

My doctor confirmed I have malignant mesothelioma.

I am fully active or can carry out light work.

I am willing to undergo genetic testing for the study.

Exclusion Criteria

I still have side effects from past cancer treatments.

I have spinal cord compression.

Participation in another clinical study where the patient received a study drug in the last month

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Olaparib is administered orally in 28-day cycles. Patients attend the clinic on days 1 and 15 of the first cycle, then every 4 weeks until treatment discontinuation.

Up to 2 years

Clinic visits on days 1 and 15 of the first cycle, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview Researchers are testing Olaparib on mesothelioma patients with gene mutations that affect DNA repair. The goal is to see if it shrinks or stabilizes tumors. Patients will take this drug orally as part of their treatment regimen.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

Olaparib will be given orally to patients in 28-day cycles. Patients will attend the clinic on days 1 (first day of treatment) and 15 of the first cycle following the beginning of study treatment and then every 4 weeks (day 1 of every cycle) until discontinuation of treatment.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

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

A new imaging agent based on the Olaparib scaffold was successfully developed and labeled with Cu-64, achieving over 90% yield and high purity, making it suitable for PET imaging of mesothelioma.

The PET imaging showed significantly higher tumor uptake in the study group compared to the control group, indicating the potential of this Olaparib-based agent for targeted diagnosis and treatment of mesothelioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma. Huang, T., Hu, P., Banizs, AB., et al.[2018]

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]

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]

The NERO trial is evaluating the efficacy of the PARP inhibitor niraparib in 84 relapsed mesothelioma patients, aiming to improve progression-free survival compared to active symptom control alone.

This study builds on previous findings that showed 15% of mesothelioma patients had durable responses to PARP inhibition, indicating potential for niraparib to offer a new treatment option in a patient population with limited therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres. Fennell, D., Griffiths, D., Eminton, Z., et al.[2023]

Cisplatin and pemetrexed are the standard treatment for unresectable malignant pleural mesothelioma, but traditional chemotherapy has only modest palliative effects.

Emerging treatments like HDAC inhibitors, specifically vorinostat, show early promise in improving outcomes for patients with advanced mesothelioma and are currently being tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the treatment of malignant pleural mesothelioma. Ramalingam, SS., Belani, CP.[2022]

Malignant mesothelioma is a challenging cancer primarily caused by environmental factors like asbestos, and most patients are not suitable for surgery or radiation, leaving cytotoxic agents as the main treatment option.

Recent trials have shown that pemetrexed, when combined with cisplatin, can achieve a response rate of 14.1% and a 1-year survival rate of 47.8%, indicating potential efficacy in treating this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging insights into the biology and therapy of malignant mesothelioma. Vogelzang, NJ.[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 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]

Malignant pleural mesothelioma (MPM) is a rare but increasing cancer linked to asbestos exposure, with a significantly higher incidence in occupationally exposed populations (100 cases/million/year) compared to the general population (1 case/million/year).

First-line treatment for MPM involves a combination of pemetrexed and cisplatin, which has been shown to improve overall survival and quality of life in phase 3 trials, while ongoing studies are exploring the potential of antiangiogenic agents like bevacizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update]. Porret, E., Madelaine, J., Galateau-Sallé, F., et al.[2008]

In a phase II trial involving 34 patients with malignant pleural mesothelioma, single-agent pazopanib did not achieve the primary endpoint of progression-free survival at 6 months, with only 28.6% of patients remaining progression-free.

Pazopanib was poorly tolerated, with 67.6% of patients experiencing grade 3 or higher adverse events, indicating a need for better strategies to target angiogenesis in mesothelioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pazopanib in Patients with Malignant Pleural Mesothelioma: NCCTG N0623 (Alliance). Parikh, K., Mandrekar, SJ., Allen-Ziegler, K., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8502774/

Phase 2 Study of Olaparib in Malignant Mesothelioma and ... In this study, we find that olaparib monotherapy has limited antitumor activity in mesothelioma patients, with an ORR of 4%, median PFS of 3.6 months, and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03531840

Olaparib in People With Malignant Mesothelioma Background: The drug olaparib may stop cancer cells from fixing damage to their deoxyribonucleic acid (DNA). It has been approved to treat certain cancers ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.9054

Phase II study of olaparib in malignant mesothelioma (MM) ... Conclusions: Olaparib has limited anti-tumor activity in previously treated MM patients including those with germline or somatic BAP1 mutations.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34661178/

Phase 2 Study of Olaparib in Malignant Mesothelioma and ... Olaparib has limited activity in previously treated mesothelioma including patients with BAP1 mutations. Germline BAP1 mutations were ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04515836

NCT04515836 | Olaparib in Patients With HRD Malignant ... To determine the percentage of patients with mesothelioma tumors (containing certain gene/cell mutations) that shrink or stop growing as a response to olaparib.

6. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/olaparib-astrazeneca-malignant-mesothelioma-likelihood-of-approval/

Olaparib by AstraZeneca for Malignant Mesothelioma Olaparib is under clinical development by AstraZeneca and currently in Phase II for Malignant Mesothelioma. According to GlobalData, Phase ...

7. researchgate.net researchgate.net/publication/354668817_Phase_2_Study_of_Olaparib_in_Malignant_Mesothelioma_and_Correlation_of_Efficacy_with_Germline_or_Somatic_Mutations_in_BRCA1_associated_protein-1_gene

Phase 2 Study of Olaparib in Malignant Mesothelioma and ... ... Olaparib was safe with no. new safety concerns. Conclusions: Olaparib has limited activity in previously. treated mesothelioma including ...

8. withpower.com withpower.com/trial/phase-3-mesothelioma-1-2021-d6bde

Olaparib for Mesothelioma Prior Safety DataThis treatment has passed at least one previous human trial. Approved in 2 JurisdictionsThis treatment is already approved in other countries ...