Clinical Trials /

Olaparib in Patients With HRD Malignant Mesothelioma

NCT04515836

Description:

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.

Related Conditions:
  • Malignant Mesothelioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib in Patients With HRD Malignant Mesothelioma
  • Official Title: Phase II Trial of Olaparib in Homologous Recombination Deficient (HRD) Malignant Mesothelioma

Clinical Trial IDs

  • ORG STUDY ID: IRB20-0117
  • NCT ID: NCT04515836

Conditions

  • Mesothelioma
  • Homologous Recombination Deficiency

Interventions

DrugSynonymsArms
OlaparibLynparzaTreatment Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Treatment ArmExperimentalOlaparib 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.
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  Women who are postmenopausal and wish to participate in the study, must also show
             evidence of postmenopausal status. Postmenopausal status will be defined as: 1) A
             woman who does not experience menstruation (known as amenorrhea) for 1 year or more
             following the end of hormonal treatments. 2) Women who have reproductive/hormone
             levels in the post-menopausal range for women under 50 as confirmed by medical tests;
             3) Radiation-induced oophorectomy (removal of one or more ovaries) with last menses
             greater than 1 year ago; 4) Menopause caused by chemotherapy with greater than 1 year
             since last menses 5) Surgical sterilization (bilateral oophorectomy or hysterectomy).

          -  Male patients must use a condom during treatment and for 3 months after the last dose
             of study drug (olaparib) when having sexual intercourse with a pregnant woman or with
             a woman of childbearing potential. Female partners of male patients should also use a
             highly effective form of contraception if they are of childbearing potential.

          -  NOTE 1: Tests to confirm the eligibility of participants who have the above mutations
             (altered germ or somatic cells) will take place at a germline or tumor sequencing lab
             that is certified under the Clinical Laboratory Improvement Amendments (CLIA).
             Eligibility of study participants will be confirmed once the physical leading this
             study receives the official mutation report from the lab and confirms that the
             participant's identified mutation fits the definition outlined above. All other
             patients must consent to tumor and normal sample sequencing as described in study
             procedures below during the prescreening phase to determine eligibility.

          -  NOTE 2: Rare exceptions of participants who may have conflicting evidence regarding
             protein function will be interpreted on an individual basis by the physician leading
             the study.

        Exclusion criteria:

        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):

          -  Any previous treatment with a type of drug/substance called a PARP inhibitor (which
             stands for poly-ADP ribose polymerase inhibitor), including olaparib.

          -  Receipt of any systemic chemotherapy or radiotherapy (except for palliative reasons)
             within 3 weeks prior to study treatment.

          -  Patients who are using strong cancer drugs called CYP3A inhibitors (also called
             Cytochrome P-450) for treatment (eg. itraconazole, telithromycin, clarithromycin,
             protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir,
             nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin,
             erythromycin, diltiazem, fluconazole, verapamil). Any treatment previously taken by
             the patient must be washed out of the patient's system 2 weeks before taking olaparib
             in this study.

          -  Patients who are using known strong CYP3A inducers (drugs for cancer patients
             including phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine,
             carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg.
             bosentan, efavirenz, modafinil). Any patients taking enzalutamide must have the drug
             washed out of their system 5 weeks before stating olaparib in this study; patients
             taking phenobarbital and other agents must have the drug washed out of their system 3
             weeks before taking olaparib in this study.

          -  Major surgery within 2 weeks of starting study treatment; patients must have recovered
             from any effects of any major surgery.

          -  Previous allogenic bone marrow transplant or double umbilical cord blood
             transplantation (dUCBT).

        Prior/concurrent clinical study experience:

          -  Participation in another clinical study where the patient received a study drug in the
             last month before starting this study.

          -  Patients with a known hypersensitivity to olaparib or any of the ingredients in the
             product.

        Other exclusions:

          -  Involvement in the planning and/or conduct of the study.

          -  The lead study physician deciding that the patient should not participate in the study
             if the patient is unlikely to follow study procedures, restrictions and requirements.

          -  Pregnant or breast-feeding women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate of Patients to Olaparib
Time Frame:Two years.
Safety Issue:
Description:To determine the response rate/percentage of patients with mesothelioma tumors (containing certain gene/cell mutations) that shrink or stop growing as a response to olaparib.

Secondary Outcome Measures

Measure:Overall Survival of Patients Taking Olaparib
Time Frame:Three years.
Safety Issue:
Description:To determine the length of time patients on the study are still alive after taking olaparib.
Measure:Progression-Free Survival of Patients Taking Olaparib
Time Frame:Two years.
Safety Issue:
Description:To determine the length of time patients taking olaparib can live with mesothelioma without their cancer getting worse.
Measure:Number of Participants With Reported Treatment-Emergent Adverse Events Based on NCI CTCAE 5
Time Frame:Two years.
Safety Issue:
Description:To quantify the number and percentage of subjects with reported toxicities/treatment-emergent adverse events (TEAEs). The frequencies of treatment-emergent adverse events will be quantified by attribution, type and grade. Adverse events will be graded using the NCI CTCAE (version 5). The number and percent of subjects with any TEAEs will be displayed by system organ class and preferred term for each treatment group. Within each preferred term, subjects will be counted only once if they had more than one event reported during the treatment period. The same summary will be performed for all serious TEAEs and all TEAEs causing discontinuation of study drug. TEAEs will also be summarized by greatest reported severity grade (Grades 1-5) for each event preferred term.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Chicago

Trial Keywords

  • mesothelioma, lung cancer, malignant mesothelioma

Last Updated

August 10, 2020