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

Trial Summary

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.

What data supports the effectiveness of the drug Olaparib for treating mesothelioma?

Olaparib has shown promise in treating other cancers, like ovarian and breast cancer, by targeting a protein called PARP, which is also overexpressed in mesothelioma. Research suggests that Olaparib-based agents can effectively target mesothelioma tumors, indicating potential effectiveness for this condition. ^{1 2 3 4 5}

How is the drug Olaparib unique in treating mesothelioma?

Olaparib is unique for mesothelioma treatment as it is a PARP inhibitor, which targets a specific mechanism in cancer cells to prevent them from repairing their DNA, unlike traditional chemotherapy that broadly attacks rapidly dividing cells. This targeted approach is novel for mesothelioma, where treatment options are limited. ^{6 7 8 9 10}

What is the purpose of this trial?

In this study, researchers will give olaparib (a drug) to mesothelioma patients who have specific changes in their DNA (known as gene mutations). Researchers will give this drug to each patient on the study to find out if it will help the patient's tumor shrink or stop growing.

Research Team

Hedy Kindler, M.D.

Principal Investigator

University of Chicago

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 (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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma. [2018]

2. France pubmed.ncbi.nlm.nih.gov

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

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

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

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

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

6. England 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. [2023]

7. France pubmed.ncbi.nlm.nih.gov

[Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update]. [2008]

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

Recent advances in the treatment of malignant pleural mesothelioma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pazopanib in Patients with Malignant Pleural Mesothelioma: NCCTG N0623 (Alliance). [2021]

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

Emerging insights into the biology and therapy of malignant mesothelioma. [2022]