Trial Outcomes & Findings for Dabrafenib and Trametinib in People With BRAF V600E Mutation Positive Lesions in Erdheim Chester Disease (NCT NCT02281760)
NCT ID: NCT02281760
Last Updated: 2021-08-31
Results Overview
Efficacy of dabrafenib and trametinib as combination therapy in patients with BRAFV600E positive Erdheim Chester Disease based on RECIST 1.1 criteria of a partial response greater than or equal to 30% decrease in at least one target lesion size.
COMPLETED
PHASE2
9 participants
24 months
2021-08-31
Participant Flow
9 participants signed consent; 3 did not meet the inclusion/exclusion criteria and 6 were started on experimental therapy.
Participant milestones
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Dabrafenib and Trametinib in People With BRAF V600E Mutation Positive Lesions in Erdheim Chester Disease
Baseline characteristics by cohort
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 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
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Efficacy of dabrafenib and trametinib as combination therapy in patients with BRAFV600E positive Erdheim Chester Disease based on RECIST 1.1 criteria of a partial response greater than or equal to 30% decrease in at least one target lesion size.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Number of Participants With Partial Response to Dabrafenib and Trametinib
|
4 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Safety of dabrafenib and trametinib as combination therapy, or either drug as single-agent therapy among participants, as measured by the adverse event characteristics of participants. See the adverse event table for list of specific adverse events experienced.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Number of Participants With Adverse Events to Dabrafenib and/or Trametinib
|
6 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Clinical response rate to dabrafenib and trametinib combination therapy in patients as measured by the percentage of patients who met RECIST 1.1 criteria for a partial response.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Clinical Response Rate to Dabrafenib/Trametinib Combination Therapy in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease.
|
4 Participants
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Progression free survival rate using RECIST 1.1 criteria among participants during the entire study period of 24 months. Progression is defined as a 20% increase in the diameter of target lesions, or a significant increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Progression-free Survival in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease
|
5 Participants
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Overall survival rate among participants defined as the number of patients alive at the end of the 24-month study period.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Overall Survival in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease
|
6 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Disease resistance to the combination therapy during the active treatment phase of the study. Resistance is defined as evidence of disease progression per RECIST 1.1 in a participant previously exhibiting stable disease or at least a partial response according to RECIST 1.1 criteria. Also, disease progression is defined as the requirement of dosage escalation in order to maintain current efficacy.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Disease Resistance to Dabrafenib/Trametinib Combination Therapy in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All patients who received dabrafenib and trametinib as combination therapy with BRAFV600E positive Erdheim Chester Disease.
Time to response to combination therapy defined as the minimum length of time elapsed during the active treatment phase to reach at least a partial response, as defined by RECIST 1.1 criteria.
Outcome measures
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=4 Participants
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Time Response to Dabrafenib/Trametinib Combination Therapy in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease.
|
5.5 months
Interval 0.0 to 12.0
|
Adverse Events
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
Serious adverse events
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 participants at risk
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
General disorders
Hyperthermia
|
16.7%
1/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Chills
|
16.7%
1/6 • 2 Years
|
Other adverse events
| Measure |
Combination Therapy With Dabrafenib and Trametinib in Patients With ECD
n=6 participants at risk
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
100.0%
6/6 • 2 Years
|
|
Blood and lymphatic system disorders
Leukopenia
|
16.7%
1/6 • 2 Years
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
16.7%
1/6 • 2 Years
|
|
Cardiac disorders
Dyspnoea
|
16.7%
1/6 • 2 Years
|
|
Cardiac disorders
Syncope
|
16.7%
1/6 • 2 Years
|
|
Ear and labyrinth disorders
Vertigo
|
16.7%
1/6 • 2 Years
|
|
Endocrine disorders
Hyperglycaemia
|
16.7%
1/6 • 2 Years
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
2/6 • 2 Years
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
3/6 • 2 Years
|
|
Gastrointestinal disorders
Dyspepsia
|
33.3%
2/6 • 2 Years
|
|
Gastrointestinal disorders
Gingival recession
|
16.7%
1/6 • 2 Years
|
|
Gastrointestinal disorders
Lip dry
|
16.7%
1/6 • 2 Years
|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6 • 2 Years
|
|
Gastrointestinal disorders
Pharyngitis
|
16.7%
1/6 • 2 Years
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • 2 Years
|
|
General disorders
Ataxia
|
33.3%
2/6 • 2 Years
|
|
General disorders
Chills
|
100.0%
6/6 • 2 Years
|
|
General disorders
Fatigue
|
66.7%
4/6 • 2 Years
|
|
General disorders
Hyperthermia
|
100.0%
6/6 • 2 Years
|
|
General disorders
Malaise
|
33.3%
2/6 • 2 Years
|
|
Immune system disorders
Erythema nodosum
|
16.7%
1/6 • 2 Years
|
|
Immune system disorders
Skin sensitisation
|
16.7%
1/6 • 2 Years
|
|
Infections and infestations
Paronychia
|
16.7%
1/6 • 2 Years
|
|
Infections and infestations
Sweating fever
|
16.7%
1/6 • 2 Years
|
|
Infections and infestations
Urinary tract infection
|
33.3%
2/6 • 2 Years
|
|
Infections and infestations
Viral infection
|
16.7%
1/6 • 2 Years
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
2/6 • 2 Years
|
|
Investigations
Amylase increased
|
50.0%
3/6 • 2 Years
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
2/6 • 2 Years
|
|
Investigations
Blood alkaline phosphatase increased
|
33.3%
2/6 • 2 Years
|
|
Investigations
Blood cholesterol increased
|
50.0%
3/6 • 2 Years
|
|
Investigations
Blood creatine phosphokinase increased
|
50.0%
3/6 • 2 Years
|
|
Investigations
Blood creatinine increased
|
50.0%
3/6 • 2 Years
|
|
Investigations
Blood pressure increased
|
33.3%
2/6 • 2 Years
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
16.7%
1/6 • 2 Years
|
|
Investigations
Blood urea increased
|
66.7%
4/6 • 2 Years
|
|
Investigations
Cystatin C increased
|
16.7%
1/6 • 2 Years
|
|
Investigations
Gamma-glutamyltransferase increased
|
16.7%
1/6 • 2 Years
|
|
Investigations
Lipase increased
|
66.7%
4/6 • 2 Years
|
|
Investigations
Prothrombin time prolonged
|
16.7%
1/6 • 2 Years
|
|
Investigations
Red blood cells urine
|
33.3%
2/6 • 2 Years
|
|
Metabolism and nutrition disorders
Anorexia nervosa
|
16.7%
1/6 • 2 Years
|
|
Metabolism and nutrition disorders
Dehydration
|
83.3%
5/6 • 2 Years
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
16.7%
1/6 • 2 Years
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
33.3%
2/6 • 2 Years
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
16.7%
1/6 • 2 Years
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
16.7%
1/6 • 2 Years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
50.0%
3/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
16.7%
1/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
50.0%
3/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Chills
|
100.0%
6/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
16.7%
1/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
2/6 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
50.0%
3/6 • 2 Years
|
|
Nervous system disorders
Confusional state
|
16.7%
1/6 • 2 Years
|
|
Nervous system disorders
Disturbance in attention
|
33.3%
2/6 • 2 Years
|
|
Nervous system disorders
Headache
|
66.7%
4/6 • 2 Years
|
|
Nervous system disorders
Memory impairment
|
16.7%
1/6 • 2 Years
|
|
Renal and urinary disorders
Acute kidney injury
|
16.7%
1/6 • 2 Years
|
|
Renal and urinary disorders
Proteinuria
|
16.7%
1/6 • 2 Years
|
|
Renal and urinary disorders
Urosepsis
|
16.7%
1/6 • 2 Years
|
|
Reproductive system and breast disorders
Penile pain
|
16.7%
1/6 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
2/6 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
16.7%
1/6 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
16.7%
1/6 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Rash
|
100.0%
6/6 • 2 Years
|
|
Vascular disorders
Hypertension
|
33.3%
2/6 • 2 Years
|
|
Vascular disorders
Hypotension
|
33.3%
2/6 • 2 Years
|
|
Vascular disorders
Labile hypertension
|
33.3%
2/6 • 2 Years
|
|
Vascular disorders
Syncope
|
16.7%
1/6 • 2 Years
|
Additional Information
Gahl, William
National Human Genome Research Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place