Olaparib in People With Malignant Mesothelioma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03531840|
Recruitment Status : Recruiting
First Posted : May 22, 2018
Last Update Posted : July 16, 2020
The drug olaparib may stop cancer cells from fixing damage to their DNA. It has been approved to treat certain cancers in people that were born with a mutation in the BRCA gene. It has not been approved for treating mesothelioma. But some people with mesothelioma have mutations in a gene, BAP1 related to BRCA. Researchers want to see if olaparib can work in patients with mutations in this gene. They also want to see if works on mutations in other genes or patients without any mutations. They want to see if olaparib causes mesothelioma tumors to shrink.
To study the effect of olaparib on mesothelioma.
People ages 18 and older with malignant mesothelioma that has already been treated
Participants will be screened with
Sample of tumor tissue or fluid
Blood, heart, and urine tests
Scans and x-rays
Participants will give blood and tissue samples. These will be genetically tested.
The study will be done in 21-day cycles.
Participants will take tables of the study drug 2 times each day. They will get information on what food and drugs to avoid during the study. They will get information about birth control. They will keep a diary of doses and symptoms.
Participants will have blood and urine tests and scans every few weeks.
Participants will be told any important genetic testing results.
Participants will stay in the study until their disease gets worse or the participant or their doctor chooses to stop it.
About 30 days after stopping the study drug, participants will have a follow-up visit. They will have a medical history, physical exam, blood tests, and scans.
Some participants will continue to have scans every 6 weeks.
|Condition or disease||Intervention/treatment||Phase|
|Mesothelioma||Drug: Olaparib||Phase 2|
- Malignant mesothelioma is an invasive and often fatal neoplasm that arises from mesothelium that lines several organs.
- Recent studies have identified germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) which can predispose to mesothelioma
- In addition to mesothelioma, germline BAP1 mutations confer increased susceptibility for the development of several other tumors including uveal melanoma, cutaneous melanoma, renal cell cancers and possibly other cancers
- In addition to BAP1, we found several novel germline variants that have previously not been associated with risk of developing mesothelioma.
- As evidenced by recent data derived from ovarian and prostate cancer patients, mutations in DNA repair genes can define subgroups of cancer patients with distinct vulnerabilities to DNA damage response inhibitors.
- Olaparib is a PARP inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated
- Both established and patient derived mesothelioma cell lines with mutated DNA repair genes are sensitive to olaparib.
-Determine the efficacy with respect to objective response rate of olaparib in patients with malignant mesothelioma based on somatic or germline mutation status of DNA repair genes
- Patients must have progressive, histologically or cytologically confirmed malignant mesothelioma.
- Age greater than or equal to 18 years
- Patients must have received prior platinum and pemetrexed based therapies
- Adequate organ and bone marrow function
- This is a phase II, single center study of olaparib in subjects with malignant mesothelioma
- All subjects will take olaparib by mouth twice daily until disease progression or intolerable side effects
- Subjects will be assessed for safety (continuously) and efficacy (every 6 weeks)
Subjects will be analyzed in 3 separate comparison groups according to their mutation status
- Comparison Group 1: Patients with a germline mutation in DNA repair genes
- Comparison Group 2: Patients with BAP1 somatic mutations
- Comparison Group 3: Patients with neither germline mutations nor BAP 1 somatic mutations
- Up to 30 evaluable subjects will be enrolled
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Olaparib in Subjects With Malignant Mesothelioma|
|Actual Study Start Date :||July 11, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Twice daily oral olaparib
all subjects will take olaparib by mouth twice per day until disease progression or unacceptable toxicity
- objective response rate [ Time Frame: 6 months after enrollment of last patient ]Percentage of subjects overall who experienced partial or complete response. Percentage of subjects with germline DNA repair mutation who experienced partial or complete response. Percentage of subjects with BAP1 somatic mutations who experienced partial or complete response. Percentage of subjects with neither germline DNA repair mutations nor somatic BAP1 mutations who experienced partial or complete response.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03531840
|Contact: Cathy I Wagner, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Raffit Hassan, M.D.||National Cancer Institute (NCI)|