Trial Outcomes & Findings for Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery (NCT NCT03148275)
NCT ID: NCT03148275
Last Updated: 2024-11-26
Results Overview
Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. A Simon minimax sampling two-stage design will be used to estimate the objective response rate. Will be calculated along with 95% confidence intervals.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
44 participants
Primary outcome timeframe
6 months
Results posted on
2024-11-26
Participant Flow
Participant milestones
| Measure |
Treatment (Trametinib)
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Overall Study
STARTED
|
44
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
19
|
Reasons for withdrawal
| Measure |
Treatment (Trametinib)
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Overall Study
Death
|
6
|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Liver transplant
|
2
|
|
Overall Study
Patient decision
|
5
|
|
Overall Study
transition to commercial drug
|
1
|
|
Overall Study
subjects withdrew from the trial after registration, but before starting study treatment
|
2
|
Baseline Characteristics
Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery
Baseline characteristics by cohort
| Measure |
Treatment (Trametinib)
n=44 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Age, Continuous
|
54 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 6 monthsWill be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. A Simon minimax sampling two-stage design will be used to estimate the objective response rate. Will be calculated along with 95% confidence intervals.
Outcome measures
| Measure |
Treatment (Trametinib)
n=42 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Objective Response Rate
|
9.5 Percentage
Interval 3.1 to 23.5
|
SECONDARY outcome
Timeframe: From time of first dose of study medication to occurrence of radiologic tumor progression per Response Evaluation Criteria in Solid Tumors 1.1, clinical progression based on treating physician assessment or death from any cause, assessed at 6 monthsWill be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.
Outcome measures
| Measure |
Treatment (Trametinib)
n=42 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
6 Month Progression-free Survival
|
66.5 percentage of participants
Interval 53.6 to 82.5
|
SECONDARY outcome
Timeframe: From the time of first dose of study drug to occurrence of death from any cause, assessed at 2 yearsWill be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.
Outcome measures
| Measure |
Treatment (Trametinib)
n=42 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Overall Survival
|
41.1 Percentage
Interval 28.1 to 60.1
|
SECONDARY outcome
Timeframe: at 6 monthsGraded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. The rates of adverse events occurring in at least 5% of subjects and rates of grade 3-5 adverse events will be tabulated by system and term.
Outcome measures
| Measure |
Treatment (Trametinib)
n=42 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Incidence of Adverse Events
Dizziness
|
12 participants who experienced the event
|
|
Incidence of Adverse Events
Dry Mouth
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Dry Skin
|
9 participants who experienced the event
|
|
Incidence of Adverse Events
Dysgeusia
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Dyspnea
|
20 participants who experienced the event
|
|
Incidence of Adverse Events
Headache
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Hyperglycemia
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Neutrophil Count Decreased
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Non-Cardiac Chest Pain- Grade 1
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
Oral Pain
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Pain
|
8 participants who experienced the event
|
|
Incidence of Adverse Events
Productive Cough
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Pruritus
|
9 participants who experienced the event
|
|
Incidence of Adverse Events
Rash Acneiform
|
21 participants who experienced the event
|
|
Incidence of Adverse Events
Bullous dermatitis- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Cellulitis- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Chest wall pain- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Cholecystitis- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Mucositis oral- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Respiratory failure- Grade 5
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Abdominal Pain
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Alanine Aminotransferase Increased
|
8 participants who experienced the event
|
|
Incidence of Adverse Events
Alkaline Phosphatase Increased
|
8 participants who experienced the event
|
|
Incidence of Adverse Events
Alopecia
|
13 participants who experienced the event
|
|
Incidence of Adverse Events
Anemia
|
21 participants who experienced the event
|
|
Incidence of Adverse Events
Anorexia
|
11 participants who experienced the event
|
|
Incidence of Adverse Events
Anxiety
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Aspartate Aminotransferase Increased
|
13 participants who experienced the event
|
|
Incidence of Adverse Events
Blurred Vision
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Bruising
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Constipation
|
18 participants who experienced the event
|
|
Incidence of Adverse Events
Cough
|
9 participants who experienced the event
|
|
Incidence of Adverse Events
Creatinine Increased
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Dehydration
|
8 participants who experienced the event
|
|
Incidence of Adverse Events
Diarrhea
|
22 participants who experienced the event
|
|
Incidence of Adverse Events
Edema Face
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Edema Limbs
|
21 participants who experienced the event
|
|
Incidence of Adverse Events
Fatigue
|
28 participants who experienced the event
|
|
Incidence of Adverse Events
Fever
|
5 participants who experienced the event
|
|
Incidence of Adverse Events
Hypertension
|
15 participants who experienced the event
|
|
Incidence of Adverse Events
Hypoalbuminemia
|
19 participants who experienced the event
|
|
Incidence of Adverse Events
Hypocalcemia
|
11 participants who experienced the event
|
|
Incidence of Adverse Events
Hypokalemia
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Hyponatremia
|
10 participants who experienced the event
|
|
Incidence of Adverse Events
Hypotension
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
Hypoxia
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
Lymphocyte Count Decreased
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
Mucositis Oral
|
8 participants who experienced the event
|
|
Incidence of Adverse Events
Myalgia
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Nausea
|
24 participants who experienced the event
|
|
Incidence of Adverse Events
Pain In Extremity
|
9 participants who experienced the event
|
|
Incidence of Adverse Events
Palpitations
|
5 participants who experienced the event
|
|
Incidence of Adverse Events
Paresthesia
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Paronychia
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Platelet Count Decreased
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
Pleural Effusion
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
Rash Maculo-Papular
|
13 participants who experienced the event
|
|
Incidence of Adverse Events
Sinus Tachycardia
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Skin Infection
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Sore Throat
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Syncope
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Upper Respiratory Infection
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Urinary Tract Infection
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Vomiting
|
18 participants who experienced the event
|
|
Incidence of Adverse Events
Weight Gain
|
5 participants who experienced the event
|
|
Incidence of Adverse Events
Back Pain
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Fall
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Hyperkalemia
|
5 participants who experienced the event
|
|
Incidence of Adverse Events
Insomnia
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Neck pain
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Respiratory failure
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Skin ulceration
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Weight loss
|
7 participants who experienced the event
|
|
Incidence of Adverse Events
White blood cell decreased
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Acute kidney injury- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Agitation- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Alanine aminotransferase increased- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Alkaline phosphatase increased- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Altered mental status- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
ammonia high- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Anemia- Grade 3
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Anxiety- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Aspartate aminotransferase increased- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Aspiration- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Back Pain- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Colitis- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Confusion- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Constipation- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Duodenal hemorrhage- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Dysesthesia- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Dysphagia- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Dyspnea- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Edema Limbs- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Encephalopathy- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Fatigue- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Flank Pain- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Gamma-glutamyl transferase- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Gastric hemorrhage- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Heart Failure- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hemoptysis- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hepatic failure- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hyperglycemia- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hyperkalemia- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hypertension- Grade 3
|
4 participants who experienced the event
|
|
Incidence of Adverse Events
Hypoalbuminemia- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Hypoglycemia- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hyponatremia- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Hypotension- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Hypoxia- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Liver transplant- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Lung infection- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
melena- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Pleural effusion- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Pleural infection- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Pneumonitis- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Portal vein thrombosis- Grade 3
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Pulmonary hypertension- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Rash acneiform- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Rash maculo-papular- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Respiratory failure- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Skin infection- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Supraventricular tachycardia- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Syncope- Grade 3
|
3 participants who experienced the event
|
|
Incidence of Adverse Events
Tumor Pain- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Urinary tract infection- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Urine output decrease- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
weight loss- Grade 3
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Hypokalemia- Grade 4
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Obesity- Grade 4
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Platelet count decreased- Grade 4
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Respiratory failure- Grade 4
|
2 participants who experienced the event
|
|
Incidence of Adverse Events
Adult respiratory distress- Grade 5
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Cardiac arrest- Grade 5
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Death NOS- Grade 5
|
6 participants who experienced the event
|
|
Incidence of Adverse Events
Duodenal hemorrhage- Grade 5
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Stridor- Grade 5
|
1 participants who experienced the event
|
|
Incidence of Adverse Events
Upper gastrointestinal hemorrhage- Grade 5
|
1 participants who experienced the event
|
SECONDARY outcome
Timeframe: Baseline and at 6 monthsPopulation: as participants were removed from trial, the number of completed PROMIS forms decreased
Will be assessed by the National Institutes of Health Patient Reported Outcomes Measurement Information System questionnaire. Patient Reported Outcomes Measurement Information System questionnaires will be scored according to recommended standardized system and t-scores generated. A mixed model will be used to analyze change in t-scores over time. PROMIS questionnaires were scored according to recommended standardized system and T-scores. A Wilcoxon signed rank test was used to assess the change in scores/T-scores over time. Determination of change in score between timepoints only included patients that had scores at those timepoints. Pain Intensity - 3a Scale: 36.3 (no pain) - 81.8 (severe pain) Pain Interference - 4a Scale: 41.6 (no interference) - 75.6 (large interference) Pain Behavior - 7a Scale: 34.1 (had no pain) - 78.9 (always in pain) Global Mental Heath Scale: 21.2 (severe) - 67.6 (none) Global Mental Physical Scale: 16.2 (severe) - 67.7 (none)
Outcome measures
| Measure |
Treatment (Trametinib)
n=42 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Change in Patient Reported Symptoms
Pain Intensity - 3a: 4 weeks
|
52 T Score
Standard Deviation 11
|
|
Change in Patient Reported Symptoms
Pain Intensity - 3a: Baseline
|
57 T Score
Standard Deviation 12
|
|
Change in Patient Reported Symptoms
Pain Intensity - 3a: 6 months
|
49 T Score
Standard Deviation 11
|
|
Change in Patient Reported Symptoms
Pain Interference - 4a: Baseline
|
59 T Score
Standard Deviation 11
|
|
Change in Patient Reported Symptoms
Pain Interference - 4a: 4 weeks
|
54 T Score
Standard Deviation 11
|
|
Change in Patient Reported Symptoms
Pain Interference - 4a: 6 months
|
51 T Score
Standard Deviation 9
|
|
Change in Patient Reported Symptoms
Pain Behavior - 7a: Baseline
|
56 T Score
Standard Deviation 11
|
|
Change in Patient Reported Symptoms
Pain Behavior - 7a: 4 weeks
|
53 T Score
Standard Deviation 11
|
|
Change in Patient Reported Symptoms
Pain Behavior - 7a: 6 months
|
51 T Score
Standard Deviation 12
|
|
Change in Patient Reported Symptoms
Global Mental Heath (questions 2,4,5,10): Baseline
|
43 T Score
Standard Deviation 10
|
|
Change in Patient Reported Symptoms
Global Mental Heath (questions 2,4,5,10): 4 weeks
|
42 T Score
Standard Deviation 8
|
|
Change in Patient Reported Symptoms
Global Mental Heath (questions 2,4,5,10): 6 months
|
38 T Score
Standard Deviation 10
|
|
Change in Patient Reported Symptoms
Global Physical Health (questions 3,6,7,8): Baseline
|
41 T Score
Standard Deviation 10
|
|
Change in Patient Reported Symptoms
Global Physical Health (questions 3,6,7,8): 4 weeks
|
36 T Score
Standard Deviation 8
|
|
Change in Patient Reported Symptoms
Global Physical Health (questions 3,6,7,8): 6 months
|
36 T Score
Standard Deviation 9
|
SECONDARY outcome
Timeframe: From time of first dose of study medication to occurrence of radiologic tumor progression per Response Evaluation Criteria in Solid Tumors 1.1, clinical progression based on treating physicianWill be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.
Outcome measures
| Measure |
Treatment (Trametinib)
n=42 Participants
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Median Progression-free Survival
|
8.3 months
Interval 7.3 to 21.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 6 monthsMcNemar test will be used to compare the number of patients with epithelioid hemangioendothelioma progression prior to starting trametinib to the number of patients with epithelioid hemangioendothelioma progression during treatment.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 6 monthsWill be used as time-dependent variables in a Cox model to determine the association with epithelioid hemangioendothelioma survival.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 6 monthsWill be used as time-dependent variables in a Cox model to determine the association with epithelioid hemangioendothelioma survival.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 6 monthsWill be analyzed by enzyme-linked immunosorbent assay. Will be used as time-dependent variables in a Cox model to determine the association with epithelioid hemangioendothelioma survival.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 6 monthsWill be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be summarized with a scatterplot. The Pearson correlation coefficient (or Spearman, if more appropriate) will be assessed to determine the strength of the agreement. Agreement of the tumor classifications (response versus no response) will be summarized as the raw agreement and with a Kappa Statistic. The association of the change in tumor volume with survival will be evaluated in two ways. The first will be to use the change in tumor volume as a time dependent variable in a Cox model. The second will be a landmark analysis (done at either the first radiographic assessment or at the second radiographic assessment) to compare the survival of patients classified as a responder (based on tumor volume) to those who have not responded by the selected landmark time. Patients who died prior to the landmark time point will be omitted from analysis.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsWill be evaluated by fluorescence in situ hybridization.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsWill be evaluated by fluorescence in situ hybridization.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsWill be analyzed by immunohistochemistry. Descriptive statistics will be generated, and estimates for the proportion of samples with demonstrated inhibition of MAPK signaling post-treatment compared to pre-treatment will be generated along with 95% confidence intervals. Likewise, the proportion of patients with demonstrated MAPK signaling inhibition at time of disease progression will be determined with the corresponding 95% confidence interval.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Trametinib)
Serious events: 25 serious events
Other events: 42 other events
Deaths: 27 deaths
Serious adverse events
| Measure |
Treatment (Trametinib)
n=42 participants at risk
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Renal and urinary disorders
Acute Kidney Injury
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Psychiatric disorders
Altered mental status
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Investigations
Anemia
|
4.8%
2/42 • Number of events 2 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
2.4%
1/42 • Number of events 3 • data was collected over 6 years
|
|
Blood and lymphatic system disorders
Bullous dermatitis
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Cardiac disorders
Cardiac arrest
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Infections and infestations
cellulitis
|
2.4%
1/42 • Number of events 2 • data was collected over 6 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
4.8%
2/42 • Number of events 3 • data was collected over 6 years
|
|
Hepatobiliary disorders
Cholecystitis
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Gastrointestinal disorders
Colitis
|
4.8%
2/42 • Number of events 2 • data was collected over 6 years
|
|
Gastrointestinal disorders
Constipation
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
General disorders
Death NOS
|
14.3%
6/42 • Number of events 6 • data was collected over 6 years
|
|
Metabolism and nutrition disorders
Dehydration
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Gastrointestinal disorders
Duodenal hemorrhage
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Gastrointestinal disorders
Dysesthesia
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.1%
3/42 • Number of events 3 • data was collected over 6 years
|
|
General disorders
Edema limbs
|
4.8%
2/42 • Number of events 2 • data was collected over 6 years
|
|
Nervous system disorders
Encephalopathy
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
General disorders
Fever
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
General disorders
Flank pain
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Cardiac disorders
Heart Failure
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Vascular disorders
Hematoma
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Cardiac disorders
Hypotension
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.8%
2/42 • Number of events 2 • data was collected over 6 years
|
|
Renal and urinary disorders
Liver Transplant
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Infections and infestations
Lung infection
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
General disorders
Malaise
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
General disorders
Non-cardiac chest pain
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Investigations
Platelet count decreased
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.1%
3/42 • Number of events 3 • data was collected over 6 years
|
|
Infections and infestations
Pleural infection
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Infections and infestations
Pneumonitis
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Cardiac disorders
Sinus tachycardia
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Skin infection
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Vascular disorders
Superficial thrombophlebitis
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Vascular disorders
Thromboembolic event
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
2.4%
1/42 • Number of events 1 • data was collected over 6 years
|
Other adverse events
| Measure |
Treatment (Trametinib)
n=42 participants at risk
Patients received trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.
Questionnaire Administration: Ancillary studies
Trametinib: Given PO
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
3/42 • Number of events 10 • data was collected over 6 years
|
|
Investigations
Alanine aminotransferase increased
|
19.0%
8/42 • Number of events 15 • data was collected over 6 years
|
|
Investigations
Alkaline phosphatase increased
|
19.0%
8/42 • Number of events 28 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
31.0%
13/42 • Number of events 13 • data was collected over 6 years
|
|
Investigations
Anemia
|
50.0%
21/42 • Number of events 62 • data was collected over 6 years
|
|
Metabolism and nutrition disorders
Anorexia
|
26.2%
11/42 • Number of events 15 • data was collected over 6 years
|
|
Psychiatric disorders
Anxiety
|
14.3%
6/42 • Number of events 7 • data was collected over 6 years
|
|
Investigations
Aspartate aminotransferase increased
|
31.0%
13/42 • Number of events 35 • data was collected over 6 years
|
|
Eye disorders
Blurred vision
|
14.3%
6/42 • Number of events 9 • data was collected over 6 years
|
|
General disorders
Bruising
|
7.1%
3/42 • Number of events 3 • data was collected over 6 years
|
|
Gastrointestinal disorders
Constipation
|
42.9%
18/42 • Number of events 26 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.4%
9/42 • Number of events 11 • data was collected over 6 years
|
|
Investigations
Creatinine increased
|
14.3%
6/42 • Number of events 14 • data was collected over 6 years
|
|
Metabolism and nutrition disorders
Dehydration
|
19.0%
8/42 • Number of events 11 • data was collected over 6 years
|
|
Gastrointestinal disorders
Diarrhea
|
52.4%
22/42 • Number of events 43 • data was collected over 6 years
|
|
General disorders
Dizziness
|
28.6%
12/42 • Number of events 21 • data was collected over 6 years
|
|
General disorders
Dry mouth
|
14.3%
6/42 • Number of events 7 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
21.4%
9/42 • Number of events 9 • data was collected over 6 years
|
|
General disorders
Dysgeusia
|
9.5%
4/42 • Number of events 5 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
47.6%
20/42 • Number of events 27 • data was collected over 6 years
|
|
General disorders
Edema face
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
General disorders
Edema limbs
|
50.0%
21/42 • Number of events 38 • data was collected over 6 years
|
|
General disorders
Fatigue
|
66.7%
28/42 • Number of events 42 • data was collected over 6 years
|
|
General disorders
Fever
|
11.9%
5/42 • Number of events 6 • data was collected over 6 years
|
|
General disorders
Headache
|
7.1%
3/42 • Number of events 4 • data was collected over 6 years
|
|
Investigations
Hyperglycemia
|
14.3%
6/42 • Number of events 14 • data was collected over 6 years
|
|
Vascular disorders
Hypertension
|
35.7%
15/42 • Number of events 24 • data was collected over 6 years
|
|
Investigations
Hypoalbuminemia
|
45.2%
19/42 • Number of events 47 • data was collected over 6 years
|
|
Investigations
Hypocalcemia
|
26.2%
11/42 • Number of events 16 • data was collected over 6 years
|
|
Investigations
Hypokalemia
|
14.3%
6/42 • Number of events 10 • data was collected over 6 years
|
|
Investigations
Hyponatremia
|
23.8%
10/42 • Number of events 16 • data was collected over 6 years
|
|
Vascular disorders
Hypotension
|
16.7%
7/42 • Number of events 8 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
16.7%
7/42 • Number of events 8 • data was collected over 6 years
|
|
Investigations
Lymphocyte count decreased
|
16.7%
7/42 • Number of events 10 • data was collected over 6 years
|
|
General disorders
Mucositis oral
|
19.0%
8/42 • Number of events 12 • data was collected over 6 years
|
|
General disorders
Myalgia
|
7.1%
3/42 • Number of events 4 • data was collected over 6 years
|
|
Gastrointestinal disorders
Nausea
|
57.1%
24/42 • Number of events 35 • data was collected over 6 years
|
|
Investigations
Neutrophil count decreased
|
14.3%
6/42 • Number of events 9 • data was collected over 6 years
|
|
General disorders
Non-cardiac chest pain
|
16.7%
7/42 • Number of events 10 • data was collected over 6 years
|
|
General disorders
Oral pain
|
7.1%
3/42 • Number of events 6 • data was collected over 6 years
|
|
General disorders
Pain
|
19.0%
8/42 • Number of events 11 • data was collected over 6 years
|
|
General disorders
Pain in extremity
|
21.4%
9/42 • Number of events 10 • data was collected over 6 years
|
|
Vascular disorders
Palpitations
|
11.9%
5/42 • Number of events 5 • data was collected over 6 years
|
|
General disorders
Paresthesia
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Infections and infestations
Paronychia
|
9.5%
4/42 • Number of events 9 • data was collected over 6 years
|
|
Investigations
Platelet count decreased
|
16.7%
7/42 • Number of events 13 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.7%
7/42 • Number of events 10 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
7.1%
3/42 • Number of events 4 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
21.4%
9/42 • Number of events 10 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
50.0%
21/42 • Number of events 51 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
31.0%
13/42 • Number of events 23 • data was collected over 6 years
|
|
Vascular disorders
Sinus tachycardia
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Infections and infestations
Skin infection
|
14.3%
6/42 • Number of events 9 • data was collected over 6 years
|
|
General disorders
Sore throat
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Nervous system disorders
Syncope
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
9.5%
4/42 • Number of events 7 • data was collected over 6 years
|
|
Infections and infestations
Urinary tract infection
|
9.5%
4/42 • Number of events 6 • data was collected over 6 years
|
|
Gastrointestinal disorders
Vomiting
|
42.9%
18/42 • Number of events 31 • data was collected over 6 years
|
|
General disorders
Weight gain
|
11.9%
5/42 • Number of events 5 • data was collected over 6 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.5%
4/42 • Number of events 5 • data was collected over 6 years
|
|
General disorders
Fall
|
7.1%
3/42 • Number of events 3 • data was collected over 6 years
|
|
Investigations
Hyperkalemia
|
11.9%
5/42 • Number of events 7 • data was collected over 6 years
|
|
Psychiatric disorders
Insomnia
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.1%
3/42 • Number of events 3 • data was collected over 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
9.5%
4/42 • Number of events 4 • data was collected over 6 years
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
7.1%
3/42 • Number of events 5 • data was collected over 6 years
|
|
General disorders
Weight loss
|
16.7%
7/42 • Number of events 14 • data was collected over 6 years
|
|
Investigations
White blood cell decreased
|
9.5%
4/42 • Number of events 11 • data was collected over 6 years
|
Additional Information
University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
University of Michigan Rogel Cancer Center
Phone: 734-936-9499
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60