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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01024946

Recruitment Status : Completed

First Posted : December 3, 2009

Results First Posted : April 20, 2015

Last Update Posted : May 12, 2015

Sponsor:

Collaborators:

Novartis Pharmaceuticals

Dana-Farber Cancer Institute

University of Pennsylvania

Information provided by (Responsible Party):

Memorial Sloan Kettering Cancer Center

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Malignant Pleural Mesothelioma
Intervention	Drug: everolimus
Enrollment	11

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Patients Getting Everolimus
Arm/Group Description	This is a multicenter, open label, ...
Arm/Group 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. everolimus: Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity
Period Title: Overall Study
Started	11
Completed	6
Not Completed	5
Reason Not Completed
Screen Failure	3
Withdrawal by Subject	1
Adverse Event	1

Baseline Characteristics

Arm/Group Title		Patients Getting Everolimus
Arm/Group Description		This is a multicenter, open label, ...
Arm/Group 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. everolimus: Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity
Overall Number of Baseline Participants		11
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	7 63.6%
	>=65 years	4 36.4%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants
	Female	1 9.1%
	Male	10 90.9%

Outcome Measures

1.Primary Outcome


Title	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.
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0...
Description	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
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Patients Getting Everolimus
Arm/Group Description:	This is a multicenter, open label, ...
Arm/Group 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. everolimus: Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity
Overall Number of Participants Analyzed	6
Measure Type: Number Unit of Measure: participants
Stable Disease	4
Progression of Disease	2

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Patients Getting Everolimus
Arm/Group Description	This is a multicenter, open label, ...
Arm/Group 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. everolimus: Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity
All-Cause Mortality
	Patients Getting Everolimus
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events Serious Adverse Events
	Patients Getting Everolimus
	Affected / at Risk (%)	# Events
Total	3/7 (42.86%)
Blood and lymphatic system disorders
Hemorrhage/Bleeding, other ^† 1	1/7 (14.29%)	1
Gastrointestinal disorders
Constipation ^† 1	1/7 (14.29%)	2
Musculoskeletal and connective tissue disorders
Inf norm ANC/gr1/2 neut-Myositis infection(muscle) ^† 1	1/7 (14.29%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath) ^† 1	2/7 (28.57%)	2
Pneumonitis/pulmonary infiltrates ^† 1	1/7 (14.29%)	1
Ascites (non-malignant) ^† 1	1/7 (14.29%)	1
Skin and subcutaneous tissue disorders
Inf norm ANC/gr1/2 neut-Cellulitis(skin) ^† 1	1/7 (14.29%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTC-3.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Patients Getting Everolimus
	Affected / at Risk (%)	# Events
Total	6/7 (85.71%)
Blood and lymphatic system disorders
Glucose, high (hyperglycemia) ^† 1	4/7 (57.14%)	4
Hemoglobin ^† 1	2/7 (28.57%)	2
Leukocytes (total WBC) ^† 1	2/7 (28.57%)	2
Lymphopenia ^† 1	1/7 (14.29%)	1
Neutrophils/granulocytes (ANC/AGC) ^† 1	2/7 (28.57%)	2
Platelets ^† 1	1/7 (14.29%)	1
Gastrointestinal disorders
Constipation ^† 1	1/7 (14.29%)	1
General disorders
Anorexia ^† 1	1/7 (14.29%)	1
Fatigue (asthenia, lethargy, malaise) ^† 1	4/7 (57.14%)	6
Insomnia ^† 1	1/7 (14.29%)	1
Rigors/chills ^† 1	1/7 (14.29%)	1
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia) ^† 1	4/7 (57.14%)	4
ALT, SGPT ^† 1	1/7 (14.29%)	1
Sodium, low (hyponatremia) ^† 1	1/7 (14.29%)	1
Psychiatric disorders
Mood alteration - Anxiety ^† 1	1/7 (14.29%)	1
Renal and urinary disorders
Bilirubin (hyperbilirubinemia) ^† 1	1/7 (14.29%)	1
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	4/7 (57.14%)	4
Dyspnea (shortness of breath) ^† 1	4/7 (57.14%)	7
Pneumonitis/pulmonary infiltrates ^† 1	2/7 (28.57%)	2
Skin and subcutaneous tissue disorders
Dry skin ^† 1	1/7 (14.29%)	1
Rash/desquamation ^† 1	1/7 (14.29%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTC-3.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dr. Lee Krug
Organization:	Memorial Sloan Kettering Cancer Center
Phone:	646-888-4201
EMail:	krugl@mskcc.org

Layout table for additonal information

Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01024946
Other Study ID Numbers:	09-142
First Submitted:	December 2, 2009
First Posted:	December 3, 2009
Results First Submitted:	April 7, 2015
Results First Posted:	April 20, 2015
Last Update Posted:	May 12, 2015

To Top