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Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations

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ClinicalTrials.gov Identifier: NCT02352844
Recruitment Status : Completed
First Posted : February 2, 2015
Results First Posted : October 2, 2018
Last Update Posted : October 2, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Solid Malignancy
Solid Tumor
Intervention Drug: Everolimus
Enrollment 12
Recruitment Details The study opened to participant enrollment on 10/07/2015 and closed to participant enrollment on 06/28/2017.
Pre-assignment Details  
Arm/Group Title Arm 1 (Everolimus)
Hide Arm/Group Description Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle.
Period Title: Overall Study
Started 12
Completed 12
Not Completed 0
Arm/Group Title Arm 1 (Everolimus)
Hide Arm/Group Description Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle.
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 12 participants
65
(40 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
7
  58.3%
Male
5
  41.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
12
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
11
  91.7%
More than one race
0
   0.0%
Unknown or Not Reported
1
   8.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 12 participants
12
 100.0%
1.Primary Outcome
Title Response Rate (RR)
Hide Description The primary endpoint will be to describe the response rate using RECIST 1.1. Response rate will be defined as complete response (disappearance of all target lesion) plus partial response (a least a 30% decrease in the sum of diameters of target lesions).
Time Frame Completion of treatment (estimated average of 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
4 participants were not evaluable for this outcome measure as they discontinued treatment prior to disease assessment.
Arm/Group Title Arm 1 (Everolimus)
Hide Arm/Group Description:
Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle.
Overall Number of Participants Analyzed 8
Measure Type: Count of Participants
Unit of Measure: Participants
1
  12.5%
2.Secondary Outcome
Title Mutations Associated With Therapeutic Response
Hide Description -To correlate mutations in the mTOR pathway with therapeutic response with everolimus
Time Frame Completion of treatment (estimated average of 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
4 participants were not evaluable for this outcome measure as they discontinued treatment prior to disease assessment and are not evaluable for this outcome measure. Out of the 8 remaining participants, only one participant had a response (complete response to therapy) and specific mutations associated with response are described below.
Arm/Group Title Arm 1 (Everolimus)
Hide Arm/Group Description:
Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle.
Overall Number of Participants Analyzed 1
Measure Type: Count of Participants
Unit of Measure: Participants
STK11 c.375-2del
1
 100.0%
STK11 c.375-8C>G
1
 100.0%
3.Secondary Outcome
Title Genetic Changes Associated With Disease Progression
Hide Description -To investigate the genetic changes associated with disease progression following treatment with everolimus.
Time Frame Completion of treatment (estimated average of 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
  • Out of the 8 participants evaluable for response, only 6 were evaluable for this outcome measure because only 6 participants had disease progression
  • Please note that 1 participant had both NF1 c.7190C>T and NF1 c.7253C>T mutations in the sample
Arm/Group Title Arm 1 (Everolimus)
Hide Arm/Group Description:
Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle.
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
NF1 p.E8*
1
  16.7%
STK11 p.E199*
1
  16.7%
NF1 p.Y489C
1
  16.7%
STK11 exon 1 E33X
1
  16.7%
STK11 L282fs*5
1
  16.7%
NF1 c.7190C>T
1
  16.7%
NF1 c.7253C>T
1
  16.7%
Time Frame From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm 1 (Everolimus)
Hide Arm/Group Description Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle.
All-Cause Mortality
Arm 1 (Everolimus)
Affected / at Risk (%)
Total   2/12 (16.67%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm 1 (Everolimus)
Affected / at Risk (%)
Total   8/12 (66.67%) 
Cardiac disorders   
Pericardial Effusion  1  3/12 (25.00%) 
Gastrointestinal disorders   
Abdominal pain  1  2/12 (16.67%) 
Constipation  1  2/12 (16.67%) 
Nausea  1  2/12 (16.67%) 
Vomiting  1  1/12 (8.33%) 
General disorders   
Death NOS  1  1/12 (8.33%) 
Death due to progressive disease  1  1/12 (8.33%) 
Hepatobiliary disorders   
Biliary obstruction  1  1/12 (8.33%) 
Infections and infestations   
Skin infection  1  1/12 (8.33%) 
Investigations   
Blood bilirubin increased  1  1/12 (8.33%) 
Metabolism and nutrition disorders   
Hyponatremia  1  2/12 (16.67%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/12 (8.33%) 
Flank Pain  1  1/12 (8.33%) 
Generalized muscle weakness  1  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/12 (8.33%) 
Pleural effusion  1  2/12 (16.67%) 
Vascular disorders   
Portal vein thrombosis  1  1/12 (8.33%) 
Thromboembolic event  1  1/12 (8.33%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm 1 (Everolimus)
Affected / at Risk (%)
Total   12/12 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  5/12 (41.67%) 
Cardiac disorders   
Atrial fibrillation  1  2/12 (16.67%) 
Pericardial Effusion  1  2/12 (16.67%) 
Eye disorders   
Dry eye  1  1/12 (8.33%) 
Flashing lights  1  1/12 (8.33%) 
Itchy eyes  1  1/12 (8.33%) 
Gastrointestinal disorders   
Ascites  1  1/12 (8.33%) 
Constipation  1  1/12 (8.33%) 
Diarrhea  1  4/12 (33.33%) 
Dyspepsia  1  4/12 (33.33%) 
Mucositis oral  1  4/12 (33.33%) 
Nausea  1  1/12 (8.33%) 
Rectal hemorrhage  1  1/12 (8.33%) 
Vomiting  1  4/12 (33.33%) 
General disorders   
Chills  1  3/12 (25.00%) 
Edema limbs  1  2/12 (16.67%) 
Fatigue  1  4/12 (33.33%) 
Fever  1  2/12 (16.67%) 
Non-cardiac chest pain  1  1/12 (8.33%) 
Sweating  1  1/12 (8.33%) 
Injury, poisoning and procedural complications   
Bruising  1  1/12 (8.33%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/12 (8.33%) 
Alkaline phosphatase increased  1  3/12 (25.00%) 
Aspartate aminotransferase increased  1  4/12 (33.33%) 
Creatinine increased  1  1/12 (8.33%) 
Lymphocyte count decreased  1  6/12 (50.00%) 
Neutrophil count decreased  1  2/12 (16.67%) 
Platelet count decreased  1  3/12 (25.00%) 
Weight loss  1  1/12 (8.33%) 
White blood cell decreased  1  2/12 (16.67%) 
Metabolism and nutrition disorders   
Anorexia  1  3/12 (25.00%) 
Dehydration  1  2/12 (16.67%) 
Hyperglycemia  1  3/12 (25.00%) 
Hyperkalemia  1  1/12 (8.33%) 
Hypertriglyceridemia  1  1/12 (8.33%) 
Hypoalbuminemia  1  3/12 (25.00%) 
Hypocalcemia  1  3/12 (25.00%) 
Hypokalemia  1  3/12 (25.00%) 
Hyponatremia  1  3/12 (25.00%) 
Musculoskeletal and connective tissue disorders   
Arthritis  1  1/12 (8.33%) 
Generalized muscle weakness  1  1/12 (8.33%) 
Myalgia  1  1/12 (8.33%) 
Pain in extremity  1  1/12 (8.33%) 
Trismus  1  1/12 (8.33%) 
Nervous system disorders   
Dizziness  1  1/12 (8.33%) 
Headache  1  1/12 (8.33%) 
Psychiatric disorders   
Agitation  1  1/12 (8.33%) 
Anxiety  1  1/12 (8.33%) 
Confusion  1  1/12 (8.33%) 
Depression  1  1/12 (8.33%) 
Insomnia  1  1/12 (8.33%) 
Renal and urinary disorders   
Acute kidney injury  1  1/12 (8.33%) 
Urinary frequency  1  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/12 (16.67%) 
Dyspnea  1  1/12 (8.33%) 
Hemoptysis  1  1/12 (8.33%) 
Nasal congestion  1  2/12 (16.67%) 
Pleural effusion  1  1/12 (8.33%) 
Postnasal drip  1  1/12 (8.33%) 
Productive cough  1  1/12 (8.33%) 
Skin and subcutaneous tissue disorders   
Nail changes  1  1/12 (8.33%) 
Pruritus  1  1/12 (8.33%) 
Purpura  1  1/12 (8.33%) 
Rash acneiform  1  2/12 (16.67%) 
Vascular disorders   
Hypertension  1  5/12 (41.67%) 
Thromboembolic event  1  1/12 (8.33%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Saiama Waqar, M.D.
Organization: Washington University School of Medicine
Phone: 314-362-5737
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02352844     History of Changes
Other Study ID Numbers: 201502067
First Submitted: January 28, 2015
First Posted: February 2, 2015
Results First Submitted: July 18, 2018
Results First Posted: October 2, 2018
Last Update Posted: October 2, 2018