Malignant Pleural MesotheliomaPhase 2NCT01024946
Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
A Phase 2 study testing everolimus in people with Malignant Pleural Mesothelioma, run by Memorial Sloan Kettering Cancer Center at 3 sites in United States.
Trial summary
For patients with malignant pleural mesothelioma that has grown despite treatment with standard chemotherapy, no treatment has yet proven beneficial. The purpose of this study is to find out what effects, both good and bad, that everolimus has on the cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2009to Jul 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
About this study
Official title: Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
For patients with malignant pleural mesothelioma that has grown despite treatment with standard chemotherapy, no treatment has yet proven beneficial. The purpose of this study is to find out what effects, both good and bad, that everolimus has on the cancer. Everolimus works by blocking a protein that helps the cancer grow. The goal of this clinical research study is to learn if the study drug everolimus can shrink or slow the growth of mesothelioma. The safety of this drug will also be studied. The patients' physical state, changes in the size of the tumor, and laboratory findings taken during the study will help us decide if everolimus is safe and effective.
Read the detailed description
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.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- everolimus
- Keywords
- mesothelioma, pleural, RAD001, Everolimus, 09-142, thoracic, lung, epithelioid, sarcomatoid
- Medical subject headings
- Mesothelioma, Malignant, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Pts getting everolimus | Experimental | 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. Receives: Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lee Krug, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01024946
- Sponsor's protocol ID
- 09-142
- Status last verified
- Apr 2015
- First submitted
- 2 Dec 2009
- Last updated
- 12 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
- ClinicalTrials.gov ID
- NCT01024946
- Acronym / sponsor ID
- 09-142
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- mesothelioma, pleural, RAD001, Everolimus, 09-142, thoracic, lung, epithelioid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Dana-Farber Cancer Institute, University of Pennsylvania
- Study start
- Dec 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 3 Dec 2009 (estimated)
- Results
- Posted 20 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For patients with malignant pleural mesothelioma that has grown despite treatment with standard chemotherapy, no treatment has yet proven beneficial. The purpose of this study is to find out what effects, both good and bad, that everolimus has on the cancer. Everolimus works by blocking a protein that helps the cancer grow. The goal of this clinical research study is to learn if the study drug everolimus can shrink or slow the growth of mesothelioma. The safety of this drug will also be studied. The patients' physical state, changes in the size of the tumor, and laboratory findings taken during the study will help us decide if everolimus is safe and effective.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pts getting everolimus | Experimental | Drug: everolimusThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusEverolimus 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. | Drug | Pts getting everolimus |
Primary outcome
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee Krug, MD principal investigator
Memorial Sloan Kettering Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus in people with Malignant Pleural Mesothelioma, run by Memorial Sloan Kettering Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2015.