Olaparib in People With Malignant Mesothelioma

NCT03531840 | Completed Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: 18009718-C-0097
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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. ...

Conditions

Mesothelioma

Keywords

DNA Mismatch Repair; BAP1; BRCA

Outcome Measures

Primary Outcomes (5)

• Number of Participants With an Objective Response

  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.

  6 months after enrollment of last patient

• Number of Participants With Germline Deoxyribonucleic Acid (DNA) Repair Mutation Who Experienced Partial or Complete Response.

  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.

  6 months after enrollment of last patient

• Percentage of Participants With Breast Cancer Type 1 Associated Protein-1 (BAP1) Somatic Mutations Who Experienced Partial or Complete Response.

  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.

  6 months after enrollment of last patient

• 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.

  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.

  6 months after enrollment of last patient

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  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.

  Adverse events were recorded from the study start date until prior to the study completion date, approximately 27 months and 11 days.

Secondary Outcomes (1)

• Number of Participants With Dose Limiting-toxicities (DLT's)

  21 days after enrollment of last subject

Study Arms (1)

Arm 1/Olaparib

EXPERIMENTAL

Twice daily oral olaparib

Drug: Olaparib; Device: ClinOmics

Interventions

Olaparib DRUG

All subjects will take olaparib by mouth twice per day until disease progression or unacceptable toxicity

Also known as: Lynparza

Arm 1/Olaparib

ClinOmics DEVICE

Non-significant risk (NSR) device

Arm 1/Olaparib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically malignant mesothelioma confirmed by the National Cancer Institute (NCI) Laboratory of Pathology. Patients with pleural, peritoneal, pericardial or tunica vaginalis mesothelioma are eligible.
• Archival tumor samples must be available and sufficient for diagnostic and genetic testing; if archival sample insufficient for testing, subject must have lesions amenable to biopsy and be willing to undergo biopsy.
• Patients must have measurable disease.
• Patients must have progressive disease at study entry
• Patients must have received prior platinum and pemetrexed based therapies. Response to platinum is not an eligibility criterion for enrollment.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of olaparib in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1.
• Patients must have a life expectancy of greater than or equal to 16 weeks
• Patients must have adequate organ and marrow function less than or equal to 5 days prior to Cycle 1 Day 1 (C1D1) as defined below:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to greater than or equal to 1,500/mcL without growth factor support
• platelets greater than or equal to 100,000/mcL
• hemoglobin greater than or equal to 10 g/dL with no blood transfusion in the past 28 days
• total bilirubin less than or equal to 1.5 x upper limits of normal (ULN) (unless Gilbert's Disease)
• Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) Serum glutamic-pyruvic transaminase (SGPT) less than or equal to 2.5 X institutional upper limit of normal (less than or equal to 5 X ULN in the presence of liver metastases)

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Patients who have received any previous treatment with a Poly (ADP-ribose) polymerase (PARP) inhibitor, including olaparib.
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Patients with other malignancy documented as occurring within the last 1 year except: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) documented as curatively treated or under control for greater than or equal to 1 year.
• Patients with features suggestive of Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) on peripheral blood smear.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to olaparib or its excipients.
• Patients who have had a whole blood transfusion within 120 days prior to enrollment. (Packed red blood cells and platelet transfusions are acceptable)
• Patients with persistent toxicities (greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 2) with the exception of alopecia,caused by previous cancer therapy
• Concomitant use of known strong or moderate cytochrome P450, family 3 (CYP3A) inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong CYP3A inducers (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Resting electrocardiogram (ECG) with Fridericia's formula (QTcF) \> 470 msec on 2 or more time points within a 24-hour period or family history of long Q wave, T wave (QT) syndrome
• Patients that have had major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mesothelioma

Interventions

olaparib

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Results Point of Contact

• Title: Dr. Raffit Hassan
• Organization: National Cancer Institute

raffit_hassan@nih.gov

240-760-6232

Study Officials

• Raffit Hassan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: May 22, 2018
• Study Start: July 11, 2018
• Primary Completion: December 4, 2019
• Study Completion: October 21, 2020
• Last Updated: April 9, 2021
• Results First Posted: March 11, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)