Trial Outcomes & Findings for Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases (NCT NCT02230306)
NCT ID: NCT02230306
Last Updated: 2017-10-12
Results Overview
Change in overall size of the sum of diameters from baseline of up to 5 intracranial target lesions in response to study treatment, achieved by individual patients.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
5 participants
Primary outcome timeframe
Until disease progression, less than or equal to 5 years.
Results posted on
2017-10-12
Participant Flow
Participant milestones
| Measure |
Cobimetinib in Combination With Vemurafenib
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Overall Study
STARTED
|
5
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Cobimetinib in Combination With Vemurafenib
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Overall Study
Did not receive study treatment
|
1
|
Baseline Characteristics
Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases
Baseline characteristics by cohort
| Measure |
Cobimetinib in Combination With Vemurafenib
n=5 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Age, Customized
Patient 1
|
26 years
n=5 Participants
|
|
Age, Customized
Patient 2
|
65 years
n=5 Participants
|
|
Age, Customized
Patient 3
|
31 years
n=5 Participants
|
|
Age, Customized
Patient 4
|
33 years
n=5 Participants
|
|
Age, Customized
Patient 5
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Until disease progression, less than or equal to 5 years.Population: Patients who received study treatment and were assessed by MRI every 8 weeks.
Change in overall size of the sum of diameters from baseline of up to 5 intracranial target lesions in response to study treatment, achieved by individual patients.
Outcome measures
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Objective Intracranial Response (OIRR)
Patient #1
|
-2.01 centimeters
|
|
Objective Intracranial Response (OIRR)
Patient #2
|
-0.8 centimeters
|
|
Objective Intracranial Response (OIRR)
Patient #4
|
-2.12 centimeters
|
|
Objective Intracranial Response (OIRR)
Patient #5
|
0.6 centimeters
|
SECONDARY outcome
Timeframe: Until disease progression, less than or equal to 5 years.Population: Patients who received study treatment and were assessed by MRI every 8 weeks.
Response to study treatment achieved by individual patients as indicated by an overall change in size of the sum of diameters from baseline of up to 5 intracranial target lesions and up to 5 extracranial target lesions.
Outcome measures
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Overall Response
Patient #1
|
-6.61 centimeters
|
|
Overall Response
Patient #2
|
-5.3 centimeters
|
|
Overall Response
Patient #4
|
-9.12 centimeters
|
|
Overall Response
Patient #5
|
-0.4 centimeters
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: Patients who received study treatment and were assessed by MRI every 8 weeks.
Time (number of months) from first documented evidence of overall Complete Response (CR) or Partial Response (PR) until time of first documented disease progression or death due to any cause (for individual patients). Progression as defined by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) is a ≥ 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm.
Outcome measures
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Progression-free Survival (PFS)
Patient #1
|
3.7 months
|
|
Progression-free Survival (PFS)
Patient #2
|
3.7 months
|
|
Progression-free Survival (PFS)
Patient #4
|
5.8 months
|
|
Progression-free Survival (PFS)
Patient #5
|
1.7 months
|
SECONDARY outcome
Timeframe: Up to 5 yearsNumber of months of survival for individual patients.
Outcome measures
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Overall Survival (OS)
Patient #1
|
7.3 months
|
|
Overall Survival (OS)
Patient #2
|
4.2 months
|
|
Overall Survival (OS)
Patient #4
|
5.8 months
|
|
Overall Survival (OS)
Patient #5
|
5.4 months
|
SECONDARY outcome
Timeframe: Until disease progression, less than or equal to 5 years.Population: Patients for whom response duration data was obtainable in those that received MRI tumor assessments every 8 weeks.
Change in relative apparent diffusion coefficient (rADC) as measured by MRI as early predictor of response value/result for each patient
Outcome measures
| Measure |
Cobimetinib in Combination With Vemurafenib
n=3 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Duration of Response
Patient #2
|
1.8 months
|
|
Duration of Response
Patient #1
|
1.6 months
|
|
Duration of Response
Patient #4
|
2.1 months
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: Data were not able to be collected and thus zero participants were analyzed for this outcome.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: Zero participants were analyzed for this outcome.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 5 yearsThe Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 scales. The brain subscale is usually used along with the core (general) questionnaire that includes 27 items. The measure yields information about total QOL, as well as information about the dimensions of physical well-being, social/family well-being, emotional well being, functional well-being, and disease-specific concerns. Patients rate all 5 items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher QOL. Items are totaled to produce the following subscales, along with an overall QOL score: physical well-being (7 items); social/family well-being (7 items); emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items). Scoring range is 0-200.
Outcome measures
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 Participants
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #4 - Cycle 2
|
97 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #1 - Cycle 1
|
107 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #1 - Cycle 2
|
84 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #1 - Cycle 3
|
110 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #1 - Cycle 4
|
97 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #2 - Cycle 1
|
83 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #2 - Cycle 2
|
91 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #2 - Cycle 3
|
104 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #2 - Cycle 4
|
95 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #4 - Cycle 1
|
98 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #4 - Cycle 3
|
95 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #4 - Cycle 4
|
101 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #4 - Cycle 5
|
119 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #4 - Cycle 6
|
98 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #5 - Cycle 1
|
69 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #5 - Cycle 2
|
103 scores on a scale
|
|
Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)
Patient #5 - Cycle 3
|
104 scores on a scale
|
Adverse Events
Cobimetinib in Combination With Vemurafenib
Serious events: 4 serious events
Other events: 4 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 participants at risk
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Infections and infestations
Papulopustular rash
|
25.0%
1/4
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
1/4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)
|
25.0%
1/4
|
|
Nervous system disorders
Hydrocephalus
|
25.0%
1/4
|
|
Psychiatric disorders
Confusion
|
25.0%
1/4
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
25.0%
1/4
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
50.0%
2/4
|
Other adverse events
| Measure |
Cobimetinib in Combination With Vemurafenib
n=4 participants at risk
Vemurafenib (960 mg twice a day) taken on Days 1 - 28 of each 28-day treatment cycle. Cobimetinib (60 mg once a day) taken on Days 1 - 21 of each 28-day treatment cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
75.0%
3/4
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
25.0%
1/4
|
|
Cardiac disorders
Chest pain - cardiac
|
25.0%
1/4
|
|
Cardiac disorders
Sinus tachycardia
|
25.0%
1/4
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify
|
25.0%
1/4
|
|
Ear and labyrinth disorders
Ear pain
|
50.0%
2/4
|
|
Ear and labyrinth disorders
Hearing impaired
|
25.0%
1/4
|
|
Ear and labyrinth disorders
Tinnitus
|
25.0%
1/4
|
|
Eye disorders
Blurred vision
|
50.0%
2/4
|
|
Eye disorders
Photophobia
|
25.0%
1/4
|
|
Eye disorders
Retinal detachment
|
25.0%
1/4
|
|
Eye disorders
Retinopathy
|
25.0%
1/4
|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
2/4
|
|
Gastrointestinal disorders
Bloating
|
25.0%
1/4
|
|
Gastrointestinal disorders
Constipation
|
50.0%
2/4
|
|
Gastrointestinal disorders
Diarrhea
|
75.0%
3/4
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4
|
|
Gastrointestinal disorders
Toothache
|
25.0%
1/4
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
2/4
|
|
General disorders
Chills
|
25.0%
1/4
|
|
General disorders
Edema face
|
25.0%
1/4
|
|
General disorders
Edema limbs
|
75.0%
3/4
|
|
General disorders
Fatigue
|
75.0%
3/4
|
|
General disorders
Fever
|
25.0%
1/4
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify
|
25.0%
1/4
|
|
Investigations
Alanine aminotransferase increased
|
50.0%
2/4
|
|
Investigations
Alkaline phosphatase increased
|
50.0%
2/4
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
2/4
|
|
Investigations
Blood bilirubin increased
|
25.0%
1/4
|
|
Investigations
CPK increased
|
50.0%
2/4
|
|
Investigations
Cholesterol high
|
25.0%
1/4
|
|
Investigations
Creatinine increased
|
50.0%
2/4
|
|
Investigations
GGT increased
|
25.0%
1/4
|
|
Investigations
Investigations - Other, specify
|
100.0%
4/4
|
|
Investigations
Lipase increased
|
25.0%
1/4
|
|
Investigations
Lymphocyte count decreased
|
50.0%
2/4
|
|
Investigations
Lymphocyte count increased
|
25.0%
1/4
|
|
Investigations
Platelet count decreased
|
50.0%
2/4
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
1/4
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
50.0%
2/4
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
1/4
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
50.0%
2/4
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
75.0%
3/4
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
50.0%
2/4
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
25.0%
1/4
|
|
Metabolism and nutrition disorders
Hypokalemia
|
75.0%
3/4
|
|
Metabolism and nutrition disorders
Hyponatremia
|
100.0%
4/4
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
100.0%
4/4
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
50.0%
2/4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify
|
50.0%
2/4
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.0%
1/4
|
|
Nervous system disorders
Dizziness
|
50.0%
2/4
|
|
Nervous system disorders
Headache
|
100.0%
4/4
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
25.0%
1/4
|
|
Nervous system disorders
Seizure
|
25.0%
1/4
|
|
Nervous system disorders
Sinus pain
|
25.0%
1/4
|
|
Psychiatric disorders
Confusion
|
50.0%
2/4
|
|
Psychiatric disorders
Insomnia
|
25.0%
1/4
|
|
Renal and urinary disorders
Proteinuria
|
25.0%
1/4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
25.0%
1/4
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
50.0%
2/4
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
25.0%
1/4
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
25.0%
1/4
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.0%
1/4
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
25.0%
1/4
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
75.0%
3/4
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
75.0%
3/4
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
50.0%
2/4
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
75.0%
3/4
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
75.0%
3/4
|
|
Vascular disorders
Flushing
|
25.0%
1/4
|
|
Vascular disorders
Hypertension
|
50.0%
2/4
|
|
Vascular disorders
Hypotension
|
25.0%
1/4
|
Additional Information
Melissa Burgess, MD
University of Pittsburgh Cancer Institute
Phone: 412-623-7277
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place