Trial Outcomes & Findings for Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity (NCT NCT01024946)
NCT ID: NCT01024946
Last Updated: 2015-05-12
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
11 participants
Primary outcome timeframe
16 weeks
Results posted on
2015-05-12
Participant Flow
Participant milestones
| Measure |
Patients 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.
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
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|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Patients 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.
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 Study
Screen Failure
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3
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
Baseline characteristics by cohort
| Measure |
Patients Getting Everolimus
n=11 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 16 weeksPer 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
Outcome measures
| Measure |
Patients Getting Everolimus
n=6 Participants
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
|
|---|---|
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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.
Progression of Disease
|
2 participants
|
|
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.
Stable Disease
|
4 participants
|
Adverse Events
Patients Getting Everolimus
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Patients Getting Everolimus
n=7 participants at risk
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
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
14.3%
1/7 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
28.6%
2/7 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
14.3%
1/7 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Inf norm ANC/gr1/2 neut-Myositis infection(muscle)
|
14.3%
1/7 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Inf norm ANC/gr1/2 neut-Cellulitis(skin)
|
14.3%
1/7 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemorrhage/Bleeding, other
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Ascites (non-malignant)
|
14.3%
1/7 • Number of events 1
|
Other adverse events
| Measure |
Patients Getting Everolimus
n=7 participants at risk
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
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|---|---|
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Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)
|
57.1%
4/7 • Number of events 4
|
|
Metabolism and nutrition disorders
ALT, SGPT
|
14.3%
1/7 • Number of events 1
|
|
General disorders
Anorexia
|
14.3%
1/7 • Number of events 1
|
|
Renal and urinary disorders
Bilirubin (hyperbilirubinemia)
|
14.3%
1/7 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
57.1%
4/7 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
57.1%
4/7 • Number of events 7
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
57.1%
4/7 • Number of events 6
|
|
Blood and lymphatic system disorders
Glucose, high (hyperglycemia)
|
57.1%
4/7 • Number of events 4
|
|
Blood and lymphatic system disorders
Hemoglobin
|
28.6%
2/7 • Number of events 2
|
|
General disorders
Insomnia
|
14.3%
1/7 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
28.6%
2/7 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymphopenia
|
14.3%
1/7 • Number of events 1
|
|
Psychiatric disorders
Mood alteration - Anxiety
|
14.3%
1/7 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
28.6%
2/7 • Number of events 2
|
|
Blood and lymphatic system disorders
Platelets
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
28.6%
2/7 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
14.3%
1/7 • Number of events 1
|
|
General disorders
Rigors/chills
|
14.3%
1/7 • Number of events 1
|
|
Metabolism and nutrition disorders
Sodium, low (hyponatremia)
|
14.3%
1/7 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place