Mesothelioma Olaparib Clinical Trial Targets Genetic Mutation

The mesothelioma program at University of Chicago Medicine is recruiting patients for its latest clinical trial involving olaparib, an oral chemotherapy drug targeting cancer-driven genetic mutations.

This single-center, phase II clinical trial is open to patients with either pleural mesothelioma or peritoneal mesothelioma.

Olaparib, also known by the brand name Lynparza, works by repairing or controlling specific gene mutations. It is known as a protein inhibitor and has been approved by the U.S. Food and Drug Administration for use with breast and ovarian cancers.

Mesothelioma, a rare malignancy caused by exposure to asbestos particles, may be next.

Several studies have shown that mutations of the BAP1 gene increase the risk of developing mesothelioma and favor the initial growth of the cancer cells.

However, some scientists believe the mutation also makes the cancer cells more susceptible to therapy, making it a natural target for treatments such as olaparib.

Clinical Trial Recruitment Underway

Principal investigator Dr. Hedy Lee Kindler, director of the mesothelioma program and associate vice chair for clinical research at University of Chicago Medicine, is hoping to recruit 56 patients. She was not available to provide additional insight into the clinical trial.

The study is designed primarily to measure the percentage of patients whose tumors shrink or stop growing in response to treatment. A secondary measurement will be overall survival and progression-free survival, along with treatment-related side effects.

Typically, patients with pleural mesothelioma receiving only standard chemotherapy survive less than 12 months after diagnosis.

To qualify for the clinical trial, patients must:

Those starting the clinical trial will receive olaparib orally in 28-day cycles. They must be in the clinic for the first and 15th day of the first cycle, then every four weeks until discontinuation of treatment. The drug will be taken twice daily.

Olaparib Effective with Genetic Mutations 

This recent study stems from the efficacy olaparib has shown for breast cancer patients with a genetic mutation similar to the BAP1 mutation often found with mesothelioma. The hope is that the drug will shrink the tumors.

FDA approval of olaparib for breast cancer was based on a phase III clinical trial showing a 42% reduction in tumor burden and an improvement in progression-free survival.

An earlier study at University of Florida Health using olaparib in combination with niraparib, another protein inhibitor, showed an ability to shrink mesothelioma cell lines in the laboratory.

The National Cancer Institute conducted a smaller clinical trial involving olaparib and mesothelioma patients that concluded earlier this year, but results were inconclusive.

Only 11 of the 23 patients in the study were identified as having a genetic mutation, which is the focus of the latest trial in Chicago. Just one of the 11 patients, the only one to complete the trial, had at least a partial response.

Five of those 11 patients experienced serious adverse side effects. There was one lung infection, one noncardiac chest pain and two abdominal disorders.

Several Mesothelioma Clinical Trials Ongoing in Chicago          

This latest clinical trial at the University of Chicago Medicine, which is expected to run through October 2024, is one of just 11 studies available to patients with mesothelioma.

Among the other studies being conducted in Chicago are: