- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01024946
Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana Farber Cancer Institute
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104-4283
- University of Pennsylvania
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have a histologically confirmed diagnosis of epithelioid, sarcomatoid, or mixed-type malignant pleural or peritoneal mesothelioma that is not amenable to surgery.
- Patients must have measurable disease according to the modified RECIST criteria for mesothelioma.
- Patients must have adequate tissue sample available for analysis of NF2/Merlin loss. (archived tissue block or 10 unstained slides)
- Patients must have received no more than two prior systemic therapy regimens, and at least one of the regimens must have included pemetrexed.
- Patients must be at least 18 years of age.
- Karnofsky performance status > or = to 70%.
- Adequate renal function: serum creatinine ≤ 1.5 x ULN.
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
- Signed informed consent
Patients must have adequate hepatic function as defined by:
- AST and ALT ≤ 2.5 x ULN (≤ 5x ULN in patients with liver metastases)
- Serum bilirubin ≤ 1.5 x ULN
Patients must have adequate bone marrow function as defined by:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
Exclusion Criteria:
- Patient has been previously treated with an mTOR inhibitor (sirolimus, temsirolimus, or everolimus).
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 3 weeks of the start of study drug for chemotherapy, biologics, targeted therapies, or immunologics or 2 weeks for radiation provided that patients have recovered from all associated toxicities at the time of registration
- Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
- Prior treatment with any investigational drug within the preceding 4 weeks
- Patients receiving chronic, systemic treatment with corticosteroids (except with a dosage equivalent to ≤ prednisone 20 mg) or another immunosuppressive agent. Patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first planned treatment with everolimus. Topical or inhaled corticosteroids are allowed
- Patients should not receive immunization with attenuated live vaccines within one week of study entry.
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- uncontrolled diabetes as defined by fasting serum glucose > or = to 1.5 x ULN
Severely impaired lung function as evidenced by:
o DLCO < 35% of the normal predicted value and/or O2 saturation that is ≤ 88% at rest on room air
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus)
- Patient has an active infection for which they received IV antibiotic, antiviral, or antifungal medications within 2 weeks of starting study drug.
- Patients with a "currently active" second malignancy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Pts getting everolimus
This is a multicenter, open label, phase II study of everolimus as a second or third line therapy for the treatment of advanced malignant pleural mesothelioma, which will also evaluate Merlin/NF2 loss as a biomarker to predict sensitivity to everolimus.
Patients who have disease progression after one or two prior chemotherapy regimens will be eligible.
In the first stage of this design, 19 patients will be accrued.
If 6 or less patients among the first 19 patients show clinical benefit, then the study will be terminated and declared negative.
If 7 or more patients show clinical benefit, than an additional 20 patients will be accrued to the second stage.
At the end of the study, if 17 or more patients show clinical benefit out of a total of 39 patients enrolled, the regimen will be considered worthy of further investigation.
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Everolimus will be administered at a dose of 10mg orally once daily continuously.
Dose reduction may be required depending on the type and severity of toxicity encountered.
One cycle will be considered 28 days.
Patients will have CT scans to evaluate for response after cycle 1 and cycle 2, and then every two cycles thereafter.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To Determine the Rate of Clinical Benefit (i.e. Rate of Complete or Partial Response Plus Stable Disease) at 16 Weeks for Patients With Malignant Mesothelioma Treated With Everolimus as Second or Third Line Therapy.
Time Frame: 16 weeks
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
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16 weeks
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Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Adenoma
- Neoplasms, Mesothelial
- Pleural Neoplasms
- Mesothelioma
- Mesothelioma, Malignant
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Everolimus
Other Study ID Numbers
- 09-142
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malignant Pleural Mesothelioma
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NRG OncologyNational Cancer Institute (NCI)TerminatedPleural Biphasic Mesothelioma | Pleural Epithelioid Mesothelioma | Stage I Pleural Malignant Mesothelioma AJCC v8 | Stage IA Pleural Malignant Mesothelioma AJCC v8 | Stage IB Pleural Malignant Mesothelioma AJCC v8 | Stage II Pleural Malignant Mesothelioma AJCC v8 | Stage IIIA Pleural Malignant...United States, Canada
-
University of ChicagoNational Cancer Institute (NCI)Active, not recruitingBiphasic Mesothelioma | Epithelioid Mesothelioma | Peritoneal Malignant Mesothelioma | Pleural Biphasic Mesothelioma | Pleural Epithelioid Mesothelioma | Pleural Malignant Mesothelioma | Pleural Sarcomatoid Mesothelioma | Recurrent Peritoneal Malignant Mesothelioma | Recurrent Pleural Malignant Mesothelioma and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingBiphasic Mesothelioma | Epithelioid Mesothelioma | Stage III Pleural Malignant Mesothelioma AJCC v7 | Stage I Pleural Malignant Mesothelioma AJCC v7 | Stage IA Pleural Malignant Mesothelioma AJCC v7 | Stage IB Pleural Malignant Mesothelioma AJCC v7 | Stage II Pleural Malignant Mesothelioma AJCC...United States
-
RS Oncology LLCRecruitingMesothelioma | Malignant Pleural Mesothelioma | Pleural Effusion, Malignant | Mesotheliomas Pleural | Malignant Pleural Effusion | Mesothelioma; LungUnited Kingdom
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Health Pharma Professional ResearchWithdrawnMalignant Pleural Mesothelioma, Advanced | Malignant Pleural Mesothelioma, UnresectableMexico
-
National Cancer Institute (NCI)TerminatedEpithelioid Mesothelioma | Sarcomatoid Mesothelioma | Stage IV Pleural Mesothelioma | Recurrent Malignant Mesothelioma | Stage II Pleural Mesothelioma | Stage III Pleural MesotheliomaUnited States
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National Cancer Institute (NCI)WithdrawnMalignant Pleural Mesotheliomas (Mpm) | Malignant Pleural Effusions (Mpe) | Epithelial Tumors, Malignant | Pleural Effusions, Malignant | Mesothelin (Msln)United States
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Royal Marsden NHS Foundation TrustMerck Sharp & Dohme LLCTerminatedAdvanced Malignant Pleural MesotheliomaUnited Kingdom
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National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Refractory Malignant Solid Neoplasm | Recurrent Peritoneal Malignant Mesothelioma | Recurrent Pleural Malignant Mesothelioma | Unresectable Solid Neoplasm | Advanced Pleural Malignant Mesothelioma | Advanced Peritoneal Malignant MesotheliomaUnited States
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Abramson Cancer Center at Penn MedicineRecruitingEpitheliod Malignant Pleural MesotheliomaUnited States
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