Phase II Study of Olaparib in Subjects With Malignant Mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Number of Participants With Germline Deoxyribonucleic Acid (DNA) Repair Mutation Who Experienced Partial or Complete Response.
研究概览
简要总结
Background:
The drug olaparib may stop cancer cells from fixing damage to their deoxyribonucleic acid (DNA). It has been approved to treat certain cancers in people that were born with a mutation in the breast cancer (BRCA) gene. It has not been approved for treating mesothelioma. But some people with mesothelioma have mutations in a gene, BRCA1 Associated Protein 1 (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.
Objective:
To study the effect of olaparib on mesothelioma.
Eligibility:
People ages 18 and older with malignant mesothelioma that has already been treated
Design:
Participants will be screened with
Sample of tumor tissue or fluid
Medical history
Physical exam
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.
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详细描述
Background:
- 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 breast cancer type 1 (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 deoxyribonucleic acid (DNA) repair genes can define subgroups of cancer patients with distinct vulnerabilities to DNA damage response inhibitors.
- Olaparib is a Poly (ADP-ribose) polymerase (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.
Objective:
-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
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1/Olaparib
Twice daily oral olaparib
干预措施: Olaparib (Drug)
Arm 1/Olaparib
Twice daily oral olaparib
干预措施: ClinOmics (Device)
结局指标
主要结局
Number of Participants With Germline Deoxyribonucleic Acid (DNA) Repair Mutation Who Experienced Partial or Complete Response.
时间窗: 6 months after enrollment of last patient
Number of participants with germline deoxyribonucleic acid (DNA) repair mutation who experienced partial or complete response. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.
Percentage of Subjects With Neither Germline Deoxyribonuclecic Acid (DNA) Repair Mutations Nor Somatic Breast Cancer Type 1 Associated Protein-1 (BAP1) Mutations Who Experienced Partial or Complete Response.
时间窗: 6 months after enrollment of last patient
Percentage of subjects with neither germline DNA repair mutations nor somatic BAP1 mutations who experienced partial or complete response.Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.
Number of Participants With an Objective Response
时间窗: 6 months after enrollment of last patient
Number of participants overall who experienced partial or complete response. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.
Percentage of Participants With Breast Cancer Type 1 Associated Protein-1 (BAP1) Somatic Mutations Who Experienced Partial or Complete Response.
时间窗: 6 months after enrollment of last patient
Percentage of participants with germline deoxyribonucleic acid (DNA) repair mutation who experienced partial or complete response. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
时间窗: Adverse events were recorded from the study start date until prior to the study completion date, approximately 27 months and 11 days.
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
次要结局
- Number of Participants With Dose Limiting-toxicities (DLT's)(21 days after enrollment of last subject)
研究者
Raffit Hassan, M.D.
Principal Investigator
National Cancer Institute (NCI)