Trial Summary
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.
Is the drug Olaparib a promising treatment for mesothelioma?The information provided does not specifically mention Olaparib as a treatment for mesothelioma, so we cannot determine if it is promising based on this data.123914
What safety data is available for Olaparib in treating mesothelioma?The provided research does not contain specific safety data for Olaparib (Lynparza) in the treatment of mesothelioma. The studies focus on other drugs and treatments for malignant pleural mesothelioma, such as pazopanib, pembrolizumab, and various novel agents, but do not mention Olaparib.4691012
What data supports the idea that Olaparib for Mesothelioma is an effective drug?The available research shows that Olaparib has potential as a treatment for mesothelioma. In a study using a version of Olaparib for imaging in mice with mesothelioma, the drug showed higher uptake in tumors compared to a control group, suggesting it could effectively target mesothelioma cells. However, most of the detailed effectiveness data for Olaparib comes from its use in treating other cancers, like ovarian and breast cancer, where it has been shown to improve outcomes when used as a maintenance therapy. This suggests that Olaparib might also be beneficial for mesothelioma, but more specific studies are needed to confirm its effectiveness for this condition.5781113
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop all current medications. However, you must stop using strong or moderate CYP3A inhibitors and inducers before starting olaparib. Strong CYP3A inhibitors need a 2-week washout period, and enzalutamide requires a 5-week washout. Other agents like phenobarbital need a 3-week washout. Check with the study team for specific guidance on your medications.
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 not pregnant.
My condition improves with platinum-based treatments.
I have been treated with cisplatin or carboplatin before.
My organs and bone marrow are functioning normally.
Exclusion Criteria
I have had a bone marrow or double cord blood transplant.
I still have side effects from past cancer treatments.
I have spinal cord compression.
I have been diagnosed with MDS or acute myeloid leukemia.
My cancer has spread to my brain.
I cannot swallow pills or have stomach issues affecting medication absorption.
I have not had major surgery in the last 2 weeks.
I do not have any illnesses that can't be controlled.
My condition does not improve with platinum-based chemotherapy.
I have heart conditions that are not under control.
I have a weakened immune system or active hepatitis.
I have been treated with a PARP inhibitor before.
I am not taking any strong or moderate drugs that affect liver enzymes.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Treatment ArmExperimental Treatment1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Chicago Medical CenterChicago, IL
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Who is running the clinical trial?
University of ChicagoLead Sponsor
AstraZenecaIndustry Sponsor
References
Emerging insights into the biology and therapy of malignant mesothelioma. [2022]Malignant mesothelioma is an aggressive malignancy that may be caused by environmental carcinogens (asbestos and erionite), viruses (SV40), and genetic predisposition. Pleural malignant mesotheliomas are far more common than the peritoneal variants. Diagnosis relies on radiographic studies as well as histology and molecular biologic analyses. The prognostic scoring systems of the Cancer and Leukemia Group B and the European Organization for Research and Treatment of Cancer are the most useful of those currently available. These systems rate performance status, age, histology, and hematologic parameters as the best prognostic factors for mesothelioma. Most patients with mesothelioma are not candidates for surgical or radiotherapy treatment, and cytotoxic agents are the only options. Historically, no classes or combinations of agents consistently yielded response rates over 20%. Recently, pemetrexed has been evaluated in phase I, II, and III clinical trials with promising results. The phase II trial showed an overall response rate of 14.1% with a 1-year survival rate of 47.8%. A phase III trial of cisplatin versus cisplatin and pemetrexed closed in February 2002 and a final analysis was presented in May 2002. Novel targeted agents are also being tested in clinical trials among mesothelioma patients and include drugs inhibiting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, and platelet-derived growth factor receptor.
[Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update]. [2008]Malignant pleural mesothelioma (MPM) is a rare tumour due to occupational asbestos exposure. The incidence of MPM will continue to increase until 2020-2030. The incidence reaches 100 cases/million/year in occupationally exposed populations as opposed to 1 case/million/year in the general population, leading to 800 to 1,000 cases per year in France. The molecular carcinogenesis of MPM is incompletely understood but alterations to genes NF2, c-met, WT1 RASSF and p16 have been described. These genes are involved in cell invasion and motility, cell division and apoptosis control. Histological diagnosis remains difficult and depends on immunohistochemical analysis as described by the French Mesopath group. Clinical diagnosis relies on thoracoscopy and large pleural biopsies, with increasing use of CT-PET for the evaluation of disease extent. Therapeutic strategy includes prophylactic irradiation following drainage or thoracoscopy to prevent tumour nodule development along drainage channels and puncture sites. In selected patients, extensive extra-pleural pneumonectomy can be performed with curative intent. First line chemotherapy is based on a combination of pemetrexed and cisplatin that has demonstrated an improvement in overall survival and quality of life in phase 3 trials. Antiangiogenic agents such as bevacizumab (Avastatin) may be of interest but need to be tested in phase 3 trials. The Mesothelioma Avastatin Pemetrexed Study (MAPS) is ongoing, coordinated by the French Thoracic Cancer Intergroup (IFCT).
Recent advances in the treatment of malignant pleural mesothelioma. [2022]Malignant pleural mesothelioma clinically manifests after decades of initial exposure to etiologic agents, such as asbestos, and presents with nonspecific symptoms such as dyspnea, pain, or weight loss. In patients with limited, resectable disease, surgical therapy with extrapleural pneumonectomy or pleurectomy is recommended, although, it is unclear which approach is superior. Radiation has a limited role and is used primarily for palliation. The palliative efficacy of traditional chemotherapeutic agents and combination regimens is modest at best. The combination of cisplatin and pemetrexed, a novel multitargeted antifolate agent, is the approved "standard of care" for patients with unresectable malignant pleural mesothelioma. A number of molecularly targeted agents are currently under evaluation for mesothelioma such as the Histone deacetylase (HDAC) inhibitors that have demonstrated promising anticancer activity. Vorinostat, a small molecule inhibitor of HDAC, which targets select members of class I and II HDACs, has shown early evidence of activity and is currently being evaluated in a randomized study for patients who progress with standard therapy for advanced mesothelioma. It is hoped that the HDAC inhibitors and other novel targeted agents will pave the way for improved outcomes for patients with this disease.
Novel therapies in phase II and III trials for malignant pleural mesothelioma. [2021]Mesothelioma is a rare malignancy of the pleura with limited therapeutic options. Despite the desperate need to develop better treatment for this disease, the rarity of the tumor type creates formidable challenges in clinical research. Nonetheless, several novel agents are under investigation. Most efforts are directed toward improving standard first-line therapy with pemetrexed and cisplatin, or developing effective second-line treatments. Several classes of drugs are being explored, including those that impact DNA transcription, cell-cycle progression, angiogenesis, and immune tolerance. This article describes several ongoing or recently completed phase II and III trials using novel agents vorinostat, everolimus, CBP501, MORAb-009, NGR-hTNF, WT1 vaccine, bevacizumab, cediranib, and thalidomide.
Safety evaluation of olaparib for treating ovarian cancer. [2015]Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with BRCA mutation-positive ovarian cancer (OC). A capsule formulation of the drug has recently received approval for use in this population for platinum-sensitive recurrent disease for maintenance therapy following platinum-based chemotherapy in Europe and as third- or fourth-line platinum-sensitive therapy in the USA.
Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. [2022]Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort.
Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma. [2018]Poly(ADP-ribose) polymerase (PARP) has emerged as an important molecular target for the treatment of several oncological diseases. A couple of molecular probes based on Olaparib scaffold have been developed by incorporation of F-18 or fluorophore for positron emission tomography (PET) or optical imaging in several types of tumor. PARP has been reported overexpressed in mesothelioma. We hereby synthesized an analogue of Olaparib containing DOTA moiety and radiolabeled it with Cu-64 to evaluate its utility of PET tracer for mesothelioma. The Cu-64 labeling was conveniently achieved at 90% yield with final compound at >99% radiochemistry purity. The biodistribution and PET imaging were performed at 0.5, 1, 2 and 18h to confirm the in vivo tumor targeting. The tumor uptake in study group was significant higher than that in control group (3.45±0.47% ID/g vs 2.26±0.30% ID/g) and tumor were clearly detected by PET imaging. These results suggest the feasibility to develop an Olaparib-based theranostic agent for mesothelioma.
Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.
A Phase II Study of Pazopanib in Patients with Malignant Pleural Mesothelioma: NCCTG N0623 (Alliance). [2021]Preclinical and clinical data have shown promise in using antiangiogenic agents to treat malignant pleural mesothelioma (MPM). We conducted this phase II study to evaluate the efficacy and toxicity of single-agent pazopanib in patients with MPM.
A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma. [2021]Currently, there is no optimal salvage therapy for patients with malignant pleural mesothelioma (MPM) who relapse after treatment with first-line chemotherapy. In line with the strong preclinical rationale for targeting fibroblast growth factor receptor (FGFR) signalling in malignant mesothelioma, we conducted a phase II study assessing the efficacy of AZD4547, an oral tyrosine multi-kinase FGFR 1-3 inhibitor, as a second or third-line treatment.
Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]Olaparib (Lynparza®) is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment in adults with advanced ovarian cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Originally approved as monotherapy, olaparib is also approved to be administered in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), defined by either a BRCA1/2 mutation and/or genomic instability. In phase III trials, olaparib monotherapy significantly improved progression-free survival (PFS) relative to placebo (SOLO-1), as did olaparib plus bevacizumab relative to placebo plus bevacizumab (PAOLA-1), in patients with advanced ovarian cancer who had responded to platinum-based chemotherapy. In PAOLA-1, improvements in PFS with olaparib plus bevacizumab were not seen in patients with HRD-negative tumours relative to placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.
A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma. [2023]The lack of effective therapies remains one of the main challenges for malignant pleural mesothelioma (MPM). In this perspective, drug repositioning could accelerate the identification of novel treatments. We screened 1170 FDA-approved drugs on a SV40-immortalized mesothelial (MeT-5A) and five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) cell lines. Biological assays were carried out for 41 drugs, showing the highest cytotoxicity and for whom there were a complete lack of published literature in MPM. Cytotoxicity and caspase activation were evaluated with commercially available kits and cell proliferation was assayed using MTT assay and by clonogenic activity with standard protocols. Moreover, the five most effective drugs were further evaluated on patient-derived primary MPM cell lines. The most active molecules were cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine. Except for alexidine, these drugs inhibited the clonogenic ability and caspase activation in all cancer lines tested. The proliferation was inhibited also on an extended panel of cell lines, including primary MPM cells. Thus, we suggest that cephalomannine, ouabain, thonzonium bromide, and emetine could represent novel candidates to be repurposed for improving the arsenal of therapeutic weapons in the fight against MPM.
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]Olaparib (Lynparza) is now approved for the adjuvant treatment of adult patients who have, or are suspected to have, the germline variation of BRCA-mutated human epidermal growth factor receptor 2-negative high-risk early breast cancer and who were previously treated with neoadjuvant or adjuvant chemotherapy.
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]Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma. This study met its primary endpoint with 15% of patients having durable responses exceeding 1 year. Therefore, there is a need to evaluate PARP inhibitors in relapsed mesothelioma patients, where options are limited. Niraparib is the PARP inhibitor used in NERO.