Trial Outcomes & Findings for Single-agent Cobimetinib for Adults With Histiocytic Disorders (NCT NCT02649972)
NCT ID: NCT02649972
Last Updated: 2023-11-18
Results Overview
by PET Response Criterial (PRC), with a dichotomous BOR of CR or PR versus neither of those. Assuming we use this binary endpoint of response, defined as best overall response of CR or PR versus not using the PET Response Criteria (PRC), a sample size of 18 patients provides 90% power to test the hypothesis that the response rate is promising (defined as 35% or higher) against a non-promising rate of 10% or lower.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
1 year
Results posted on
2023-11-18
Participant Flow
Participant milestones
| Measure |
Cobimetinib
This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders
|
|---|---|
|
Overall Study
STARTED
|
35
|
|
Overall Study
COMPLETED
|
34
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Cobimetinib
This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders
|
|---|---|
|
Overall Study
Not treated
|
1
|
Baseline Characteristics
Single-agent Cobimetinib for Adults With Histiocytic Disorders
Baseline characteristics by cohort
| Measure |
Cobimetinib
n=35 Participants
This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders
|
|---|---|
|
Age, Continuous
|
51 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 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
|
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
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
27 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
|
|
Region of Enrollment
United States
|
35 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 1 yearby PET Response Criterial (PRC), with a dichotomous BOR of CR or PR versus neither of those. Assuming we use this binary endpoint of response, defined as best overall response of CR or PR versus not using the PET Response Criteria (PRC), a sample size of 18 patients provides 90% power to test the hypothesis that the response rate is promising (defined as 35% or higher) against a non-promising rate of 10% or lower.
Outcome measures
| Measure |
Cobimetinib
n=35 Participants
This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders
|
|---|---|
|
Best Overall Response
Complete Metabolic Response
|
21 Participants
|
|
Best Overall Response
Partial Metabolic Response
|
5 Participants
|
|
Best Overall Response
Stable Metabolic Disease
|
3 Participants
|
|
Best Overall Response
Not evaluable
|
6 Participants
|
Adverse Events
Cobimetinib
Serious events: 10 serious events
Other events: 35 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Cobimetinib
n=35 participants at risk
This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders
|
|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
11.4%
4/35 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
2.9%
1/35 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
2/35 • 1 year
|
|
Nervous system disorders
Cognitive disturbance
|
5.7%
2/35 • 1 year
|
|
Psychiatric disorders
Confusion
|
5.7%
2/35 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
5.7%
2/35 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
2.9%
1/35 • 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
2.9%
1/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypernatremia
|
11.4%
4/35 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.7%
2/35 • 1 year
|
|
Vascular disorders
Hypotension
|
5.7%
2/35 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.6%
3/35 • 1 year
|
|
Immune system disorders
Immune system disorders - Other
|
2.9%
1/35 • 1 year
|
|
Infections and infestations
Infections and infestations - Other
|
5.7%
2/35 • 1 year
|
|
Infections and infestations
Lung infection
|
5.7%
2/35 • 1 year
|
|
Cardiac disorders
Myocardial infarction
|
2.9%
1/35 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
2.9%
1/35 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.9%
1/35 • 1 year
|
|
Cardiac disorders
Paroxysmal atrial tachycardia
|
2.9%
1/35 • 1 year
|
|
Investigations
Platelet Count Decreased
|
2.9%
1/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
2.9%
1/35 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
8.6%
3/35 • 1 year
|
|
Eye disorders
Retinal vascular disorder
|
2.9%
1/35 • 1 year
|
|
Infections and infestations
Sepsis
|
5.7%
2/35 • 1 year
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
5.7%
2/35 • 1 year
|
|
Cardiac disorders
Supraventricular tachycardia
|
2.9%
1/35 • 1 year
|
|
Nervous system disorders
Syncope
|
2.9%
1/35 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy
|
2.9%
1/35 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
8.6%
3/35 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
2/35 • 1 year
|
Other adverse events
| Measure |
Cobimetinib
n=35 participants at risk
This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders
|
|---|---|
|
Investigations
CPK Increased
|
62.9%
22/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
62.9%
22/35 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
57.1%
20/35 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
54.3%
19/35 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
45.7%
16/35 • 1 year
|
|
Investigations
Aspartate aminotransferase increasd
|
45.7%
16/35 • 1 year
|
|
General disorders
Fatigue
|
42.9%
15/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
42.9%
15/35 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
42.9%
15/35 • 1 year
|
|
Investigations
Alkaline phosphatase increaseed
|
40.0%
14/35 • 1 year
|
|
General disorders
Edema limbs
|
37.1%
13/35 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
37.1%
13/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
37.1%
13/35 • 1 year
|
|
Investigations
White blood cell decreased
|
34.3%
12/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
31.4%
11/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
31.4%
11/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
28.6%
10/35 • 1 year
|
|
Investigations
Platelet count decreased
|
28.6%
10/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.7%
9/35 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.7%
9/35 • 1 year
|
|
Investigations
Blood bilirubin increased
|
22.9%
8/35 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
22.9%
8/35 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
22.9%
8/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypernatremia
|
20.0%
7/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
20.0%
7/35 • 1 year
|
|
Investigations
Lipase increased
|
20.0%
7/35 • 1 year
|
|
Investigations
Neutrophil count decreased
|
20.0%
7/35 • 1 year
|
|
Investigations
Serum amylase increased
|
20.0%
7/35 • 1 year
|
|
Investigations
Creatinine increased
|
17.1%
6/35 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
17.1%
6/35 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
17.1%
6/35 • 1 year
|
|
Investigations
Activated partial thromboplastin time prolonges
|
14.3%
5/35 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
14.3%
5/35 • 1 year
|
|
Cardiac disorders
Ejection fraction decreased
|
14.3%
5/35 • 1 year
|
|
Nervous system disorders
Headache
|
14.3%
5/35 • 1 year
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
14.3%
5/35 • 1 year
|
|
Eye disorders
Blurred vision
|
11.4%
4/35 • 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
11.4%
4/35 • 1 year
|
|
Vascular disorders
Hypertension
|
11.4%
4/35 • 1 year
|
|
Renal and urinary disorders
Acute kidney injury
|
8.6%
3/35 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
8.6%
3/35 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.6%
3/35 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
8.6%
3/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
8.6%
3/35 • 1 year
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
8.6%
3/35 • 1 year
|
|
Infections and infestations
Mucosal infection
|
8.6%
3/35 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
8.6%
3/35 • 1 year
|
|
Eye disorders
Periorbital edema
|
8.6%
3/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.7%
2/35 • 1 year
|
|
Gastrointestinal disorders
Bloating
|
5.7%
2/35 • 1 year
|
|
Infections and infestations
Bronchial infection
|
5.7%
2/35 • 1 year
|
|
Infections and infestations
Conjunctivitis infective
|
5.7%
2/35 • 1 year
|
|
Nervous system disorders
Dizziness
|
5.7%
2/35 • 1 year
|
|
General disorders
Edema face
|
5.7%
2/35 • 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
5.7%
2/35 • 1 year
|
|
Reproductive system and breast disorders
Genital edema
|
5.7%
2/35 • 1 year
|
|
Vascular disorders
Hypotension
|
5.7%
2/35 • 1 year
|
|
Investigations
INR Increased
|
5.7%
2/35 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
2/35 • 1 year
|
|
Gastrointestinal disorders
Oral pain
|
5.7%
2/35 • 1 year
|
|
General disorders
Pain
|
5.7%
2/35 • 1 year
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.7%
2/35 • 1 year
|
|
Skin and subcutaneous tissue disorders
Purpura
|
5.7%
2/35 • 1 year
|
|
Infections and infestations
Skin infection
|
5.7%
2/35 • 1 year
|
Additional Information
Dr. Eli Diamond, MD
Memorial Sloan Kettering Cancer Center
Phone: 212-610-0243
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place