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Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity

Phase 2
18 Years
Not Enrolling
Malignant Pleural Mesothelioma

Thank you

Trial Information

Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity

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

- Patients must have measurable disease according to the modified RECIST criteria for

- 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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Time Frame:

16 weeks

Safety Issue:


Principal Investigator

Lee Krug, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

December 2009

Completion Date:

July 2012

Related Keywords:

  • Malignant Pleural Mesothelioma
  • mesothelioma
  • pleural
  • RAD001
  • Everolimus
  • 09-142
  • thoracic
  • lung
  • epithelioid
  • sarcomatoid
  • Mesothelioma



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of PennsylvaniaPhiladelphia, Pennsylvania  19104
Dana Farber Cancer InstituteBoston, Massachusetts  02115