Trial Outcomes & Findings for Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations (NCT NCT02352844)
NCT ID: NCT02352844
Last Updated: 2018-10-02
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Completion of treatment (estimated average of 6 months)
Results posted on
2018-10-02
Participant Flow
The study opened to participant enrollment on 10/07/2015 and closed to participant enrollment on 06/28/2017.
Participant milestones
| Measure |
Arm 1 (Everolimus)
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 Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations
Baseline characteristics by cohort
| Measure |
Arm 1 (Everolimus)
n=12 Participants
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.
|
|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Completion of treatment (estimated average of 6 months)Population: 4 participants were not evaluable for this outcome measure as they discontinued treatment prior to disease assessment.
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).
Outcome measures
| Measure |
Arm 1 (Everolimus)
n=8 Participants
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.
|
|---|---|
|
Response Rate (RR)
|
1 Participants
|
SECONDARY outcome
Timeframe: Completion of treatment (estimated average of 6 months)Population: 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.
-To correlate mutations in the mTOR pathway with therapeutic response with everolimus
Outcome measures
| Measure |
Arm 1 (Everolimus)
n=1 Participants
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.
|
|---|---|
|
Mutations Associated With Therapeutic Response
STK11 c.375-2del
|
1 Participants
|
|
Mutations Associated With Therapeutic Response
STK11 c.375-8C>G
|
1 Participants
|
SECONDARY outcome
Timeframe: Completion of treatment (estimated average of 6 months)Population: * 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
-To investigate the genetic changes associated with disease progression following treatment with everolimus.
Outcome measures
| Measure |
Arm 1 (Everolimus)
n=6 Participants
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.
|
|---|---|
|
Genetic Changes Associated With Disease Progression
NF1 p.E8*
|
1 Participants
|
|
Genetic Changes Associated With Disease Progression
STK11 p.E199*
|
1 Participants
|
|
Genetic Changes Associated With Disease Progression
NF1 p.Y489C
|
1 Participants
|
|
Genetic Changes Associated With Disease Progression
STK11 exon 1 E33X
|
1 Participants
|
|
Genetic Changes Associated With Disease Progression
STK11 L282fs*5
|
1 Participants
|
|
Genetic Changes Associated With Disease Progression
NF1 c.7190C>T
|
1 Participants
|
|
Genetic Changes Associated With Disease Progression
NF1 c.7253C>T
|
1 Participants
|
Adverse Events
Arm 1 (Everolimus)
Serious events: 8 serious events
Other events: 12 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Arm 1 (Everolimus)
n=12 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Hepatobiliary disorders
Biliary obstruction
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Blood bilirubin increased
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Constipation
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Death NOS
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Death due to progressive disease
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Nausea
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Cardiac disorders
Pericardial Effusion
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Vascular disorders
Portal vein thrombosis
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Infections and infestations
Skin infection
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Vascular disorders
Thromboembolic event
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
Other adverse events
| Measure |
Arm 1 (Everolimus)
n=12 participants at risk
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.
|
|---|---|
|
Investigations
Activated partial thromboplastin time prolonged
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Renal and urinary disorders
Acute kidney injury
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Psychiatric disorders
Agitation
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Alkaline phosphatase increased
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Blood and lymphatic system disorders
Anemia
|
41.7%
5/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Psychiatric disorders
Anxiety
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Ascites
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
4/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Cardiac disorders
Atrial fibrillation
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Injury, poisoning and procedural complications
Bruising
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Chills
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Psychiatric disorders
Confusion
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Creatinine increased
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Psychiatric disorders
Depression
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
4/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Eye disorders
Dry eye
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
33.3%
4/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Edema limbs
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Fatigue
|
33.3%
4/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Fever
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Eye disorders
Flashing lights
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Vascular disorders
Hypertension
|
41.7%
5/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Psychiatric disorders
Insomnia
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Eye disorders
Itchy eyes
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Lymphocyte count decreased
|
50.0%
6/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Mucositis oral
|
33.3%
4/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Neutrophil count decreased
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Non-cardiac chest pain
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Cardiac disorders
Pericardial Effusion
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Platelet count decreased
|
25.0%
3/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Skin and subcutaneous tissue disorders
Purpura
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
General disorders
Sweating
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Vascular disorders
Thromboembolic event
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Renal and urinary disorders
Urinary frequency
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
4/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
Weight loss
|
8.3%
1/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
|
Investigations
White blood cell decreased
|
16.7%
2/12 • From start of treatment through 30 days after completion of treatment (estimated average of 7 months)
|
Additional Information
Saiama Waqar, M.D.
Washington University School of Medicine
Phone: 314-362-5737
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place