Clinical Trial of Olaparib for Mesothelioma

The National Cancer Institute (NCI) will soon begin to recruit patients for a study of treatment with olaparib for mesothelioma. The two-year Phase II clinical trial (identifier NCT03531840) will examine whether a drug that is approved for treatment of advanced ovarian cancer and breast cancer can also prevent tumor progression in mesothelioma patients. Olaparib is produced by AstraZeneca and is also known by its trade name, LYNPARZA.

The potential usefulness of olaparib for mesothelioma comes down to genetic factors that may predispose some patients to certain cancers. Olaparib is particularly useful in breast cancers with a mutation in the BRCA protein. A mutation in the BAP1 (BRCA1 associated protein-1) gene is thought by some to correlate with a higher risk of developing mesothelioma among people who were exposed to asbestos. If it works for breast cancer patients, olaparib for mesothelioma could offer another avenue of treatment.

How Does Olaparib Help Cancer Patients?

To understand treatment with olaparib for mesothelioma patients, it’s helpful to have a refresher on the basics of cellular reproduction. Before a cell replicates itself, its DNA splits in two and creates a copy. The new cell will have the same DNA as the old one. If a mistake occurs in the copying process, there’s a variation in the DNA code, creating a mutation.

DNA is arranged in a double helix: a twisting ladder of paired genes. DNA strands often break or get damaged and need repairs. The proteins that perform these repairs are implicated in some types of cancers – and now in a potential cancer treatment.

Cancer cells replicate more often than normal cells, so they have a particular need to keep their DNA in good repair. Poly ADP ribose polymerase (PARP) is group of proteins whose specialty is the repair of breaks in a single strand of DNA. If there’s a break in one strand of DNA, it can turn into a complete break in the double helix when the cell tries to reproduce.

BRCA1 and BRCA2 are proteins that repair breaks in double DNA strands. When there is a mutation in the genetic code for the BRCA protein, the DNA double helix isn’t properly repaired during replication. This BRCA mutation is a factor in some cancers, particularly breast cancer.

Olaparib works by blocking PARP. Because PARP can’t repair the little dings on the DNA strands, these develop into more big breaks as cells divide. When BRCA is mutated, it’s not able to repair these broken double DNA strands and cells. This breakdown in DNA replication can keep cancer cells from reproducing themselves.

Olaparib is approved by the FDA as a single treatment for certain patients with ovarian or breast cancer. By blocking PARP, olaparib may also prevent mesothelioma tumors from growing and metastasizing.

As with so much of what happens in our cells, scientists don’t fully understand how olaparib prevents the progression of certain tumors. In clinical trials on patients with advanced ovarian cancer, more than a third of patients with BRCA mutations benefited from the drug. Almost a quarter of patients without BRCA mutations were also helped by olaparib; researchers don’t fully understand why.

With more research, including this clinical trial of olaparib for mesothelioma, scientists will continue to expand their understanding of how cancer grows – and expand treatment options for patients with mesothelioma and other cancers.

BAP1 and Olaparib for Mesothelioma

The NCI research team sees potential of olaparib for mesothelioma because a mutation in the BAP1 gene is found in some mesothelioma cancers and BAP1 is related to BRCA1. The functions of the BAP1 enzyme include suppressing the growth of tumors and suppressing metastasis. When BAP1 is damaged, it may not perform these critical functions, allowing mesothelioma tumors to form.

The upcoming Phase II mesothelioma clinical trial will look at the effectiveness of olaparib for mesothelioma patients with a BAP1 mutation. Researchers will also study the drug in mesothelioma patients who don’t have this mutation. The FDA has not yet approved olaparib for mesothelioma treatment. In this Phase II trial, there will be no control; all participants will receive the olaparib treatment.

The researchers hope to recruit 40 mesothelioma patients who have already received mesothelioma treatment. The study is open to all mesothelioma types.

Participants in the clinical trial will get 21-day cycles of treatment with olaparib. The drug is taken orally twice a day. If you are accepted into this clinical trial, you’ll need to keep a diary recording the dose of olaparib you are taking and any symptoms or side effects you experience. You’ll give blood and urine samples periodically, for lab analysis.

Part of the preparation and screening for this clinical trial is genetic testing. The researchers will share with you any genetic information they learn about you. This could be valuable information as you explore additional mesothelioma treatments or clinical trials.

The study of olaparib for mesothelioma is expected to be ongoing for two years. You can stay in the study as long as you like. Researchers expect participants to continue while the olaparib is an effective treatment for their mesothelioma. As with every clinical trial, you are free to leave at any time. If the side effects are too hard on you or if your mesothelioma progresses, you may choose to seek different treatments. Participants in this clinical trial will work with their mesothelioma doctors to determine the best course of treatment throughout the study period.

The researchers ask that all participants return for a follow-up exam about a month after stopping olaparib for mesothelioma. In addition, they may ask some study participants to have regular scans to track tumor progression.

Possible Side Effects of Olaparib for Mesothelioma

Like most cancer drugs, olaparib can have side effects. Normal side effects include digestive problems such as nausea and vomiting; excessive tiredness; achy joints; and anemia. In some patients, olaparib can cause bone marrow diseases. These diseases, Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML), can be life-threatening. Part of the intake process for the NCI clinical trial of olaparib for mesothelioma will be screening for conditions that would make you more susceptible to MDS or AML.

The researchers will inform patients of dietary recommendations while taking olaparib. Some vitamins and medicinal herbs, as well as over-the-counter medications, can interfere with the effectiveness of this cancer treatment.

If you are not a good candidate for the NCI olaparib study, there could be another mesothelioma clinical trial looking for mesothelioma patients just like you. Take a look at the clinical trial matching tool here on our website. Participating in a mesothelioma clinical trial can give you access to new treatments that aren’t yet approved, like olaparib for mesothelioma.