Olaparib in Patients With HRD Malignant Mesothelioma

NCT04515836 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB20-0117
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, researchers will give olaparib (a drug) to mesothelioma patients who have specific changes in their DNA (known as gene mutations). Researchers will give this drug to each patient on the study to find out if it will help the patient's tumor shrink or stop growing.

Conditions

Mesothelioma; Homologous Recombination Deficiency

Keywords

mesothelioma, lung cancer, malignant mesothelioma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate of Patients to Olaparib

  To determine the percentage of patients with mesothelioma tumors (containing certain gene/cell mutations) that shrink or stop growing as a response to olaparib.

  Two years.

Secondary Outcomes (3)

• Overall Survival of Patients Taking Olaparib

  Three years.

• Progression-Free Survival of Patients Taking Olaparib

  Two years.

• Frequency of Treatment-Related Side Effects/ Adverse Events

  Two years.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Olaparib will be given orally to patients in 28-day cycles. Patients will attend the clinic on days 1 (first day of treatment) and 15 of the first cycle following the beginning of study treatment and then every 4 weeks (day 1 of every cycle) until discontinuation of treatment.

Drug: Olaparib

Interventions

Olaparib DRUG

Olaparib is a chemotherapy drug (packaged as a pill) that can be taken by mouth, twice daily.

Also known as: Lynparza

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Must have a medical diagnosis of malignant mesothelioma that has been confirmed by a physician.
• Participant must be able to sign a consent form stating that they choose (of their own free will) to participate in the study and agree to follow the study requirements and restrictions that are listed in the consent form.
• Must be willing to sign and date consent form before any mandatory study-specific procedures, sample collecting and tests.
• Willing to experience genetic testing to determine study eligibility. Must be willing to genetically test tumor and normal body cells.
• Before participating in the treatment phase of this study, participants must be willing to give their own consent (agreement) to have their samples collected for genetic and biomarker research.
• Age 18 or older.
• Participant must show evidence of specific DNA changes/genetic mutations defined as follows: A) BAP1 loss (the loss of a protein called ubiquitin carboxyl-terminal hydrolase) verified by physicians at the University of Chicago using sampling tests AND/OR B) A mutation (abnormal change) in the participant's germ cells (reproductive cells) or somatic cells (non-reproductive cells) that disrupts protein function in at least one of the patient's genes.
• Prior treatment with cisplatin or carboplatin is required.
• Patients must have platinum-sensitive disease (cancer that responds to treatments with anticancer drugs containing metal platinum). For eligibility in this study, platinum-sensitive disease will be defined as no disease progression while on a platinum agent (chemotherapy drug) or for at least 3 months after completing treatment with a platinum agent.
• Patients must have normal organ and bone marrow function measured within 28 days prior to receiving study treatment. Normal bone marrow and organ function will be assessed using specific lab tests/ criteria set by the study's lead physician.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Patients must have a life expectancy of 16 weeks or more.
• Must have a tumor that can be measured according to criteria set by the modified Response Evaluation Criteria in Solid Tumors (RECIST) standards for pleural mesothelioma and RECIST 1.1 for peritoneal and tunica vaginalis mesothelioma. Patients in the study must have at least one area of damaged tissue (a lesion) that has not received previous radiation treatment. This damaged tissue must be accurately measured at the beginning of the study as greater than or equal to 10 mm in the longest diameter (except lymph nodes which must have short axis greater than or equal to 15 mm). The patient's tumor would be measured using computed tomography (CT), which is suitable for accurate repeated measurements.
• Both male and female patients can participate in this study.
• If a woman is of childbearing potential and wishes to participate in the study, she most show evidence that she is not pregnant using a negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.

You may not qualify if:

• Medical conditions:
• Any evidence of uncontrollable illness that the physician leading this study deems undesirable for the patient to participate in the trial.
• Other malignancy (tumor/cancer) unless it has been treated with no evidence of disease for 3 or more years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
• Patients with BAP1 tumor predisposition syndrome will be included in the trial. These patients may be eligible if they have a history of syndrome-related cancers, provided they completed their surgery and chemotherapy more than three years prior to registration, and the patient remains free of disease that continues to re-occur or spread to other parts of the body.
• Patients with cancer that does not respond to platinum chemotherapy drugs (known as platinum-resistant disease), defined as disease progression during or within 3 months of receiving chemotherapy.
• Resting electrocardiogram (ECG) that shows the patient has uncontrolled, potentially reversible cardiac conditions or patients with congenital long QT syndrome (a heart rhythm condition that can cause fast, chaotic heartbeats), as judged by the study's lead physician.
• Persistent toxicities (greater than the Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with findings suggestive of MDS/AML.
• Patients with cancer cells that have moved from one part of their body to the brain (brain metastases) causing the patient to show symptoms/signs of more serious illness. A scan to confirm the absence of cancerous cells in the brain 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.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-cancerous 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.
• Patients unable to swallow oral medications and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Patients who have a compromised immune system, e.g., patients who have tested positive for human immunodeficiency virus (HIV).
• Patients with known active hepatitis (i.e. Hepatitis B or C) confirmed by medical tests; patients with a past or resolved Hepatitis B infection are eligible. Patients positive for hepatitis C virus are eligible only if samples of the patient's DNA tests negative for hepatitis C, according to genetic tests (using polymerase chain reaction).
• Prior/concomitant therapy (medications/treatments that may conflict with the study drug, olaparib):

Sponsors & Collaborators

• University of Chicago: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Chicago Medical Center

Chicago, Illinois, 60615, United States

RECRUITING

MeSH Terms

Conditions

Mesothelioma; Lung Neoplasms; Mesothelioma, Malignant

Interventions

olaparib

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Pleural Neoplasms

Study Officials

• Hedy L Kindler, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hedy L Kindler, MD

CONTACT

773-702-0360; hkindler@medicine.bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2020
• First Posted: August 17, 2020
• Study Start: February 19, 2021
• Primary Completion (Estimated): April 15, 2028
• Study Completion (Estimated): April 15, 2028
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (1)