Trial Outcomes & Findings for BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma (NCT NCT01512251)
NCT ID: NCT01512251
Last Updated: 2020-08-17
Results Overview
RP2D determined by maximum tolerated dose (MTD), post-dose-limiting toxicity (DLT) period toxicity, and pharmacokinetic data
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
8 participants
Primary outcome timeframe
28 days
Results posted on
2020-08-17
Participant Flow
Participant milestones
| Measure |
Vemurafenib-Naïve
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid
Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
Vemurafenib-Resistant
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid
Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
|---|---|---|
|
Dose Level -1
STARTED
|
3
|
5
|
|
Dose Level -1
COMPLETED
|
3
|
5
|
|
Dose Level -1
NOT COMPLETED
|
0
|
0
|
|
Phase I, Dose 1
STARTED
|
3
|
5
|
|
Phase I, Dose 1
COMPLETED
|
0
|
0
|
|
Phase I, Dose 1
NOT COMPLETED
|
3
|
5
|
|
Phase I, Dose 2
STARTED
|
0
|
0
|
|
Phase I, Dose 2
COMPLETED
|
0
|
0
|
|
Phase I, Dose 2
NOT COMPLETED
|
0
|
0
|
|
Phase I, Dose 3
STARTED
|
0
|
0
|
|
Phase I, Dose 3
COMPLETED
|
0
|
0
|
|
Phase I, Dose 3
NOT COMPLETED
|
0
|
0
|
|
Phase I, Dose 4
STARTED
|
0
|
0
|
|
Phase I, Dose 4
COMPLETED
|
0
|
0
|
|
Phase I, Dose 4
NOT COMPLETED
|
0
|
0
|
|
Phase II
STARTED
|
0
|
0
|
|
Phase II
COMPLETED
|
0
|
0
|
|
Phase II
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma
Baseline characteristics by cohort
| Measure |
Vemurafenib-Naïve
n=3 Participants
|
Vemurafenib-Resistant
n=5 Participants
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44 years
n=5 Participants
|
51 years
n=7 Participants
|
50 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 daysRP2D determined by maximum tolerated dose (MTD), post-dose-limiting toxicity (DLT) period toxicity, and pharmacokinetic data
Outcome measures
| Measure |
Determination of MTD
n=8 Participants
Vemurafenib-Naïve and Vemurafenib-Resistant populations received:
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
|
Vemurafenib-Resistant
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid
Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
|---|---|---|
|
Phase 1 - Safety & Recommended Phase 2 Dose (RP2D)
|
60 mg
|
—
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Data were not collected, study never advanced to Phase II.
6 month progression-free survival rate (PFS6) determined by tumor assessments, clinical tests and laboratory tests
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 28 (+/- 3) of even-numbered treatment cycles until progressionPopulation: Data not collected
Objective response rate determined by tumor assessments, clinical tests and laboratory tests.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During study treatment, up to 2 yearsPopulation: Data not collected
Determined by clinical and laboratory tests, and adverse events (AE) assessments
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: No time limitPopulation: Data not collected
PTEN expression associated with better PFS determined by laboratory tests.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: No time limitPopulation: Data not collected: study was terminated early due to dose limiting toxicities.
Greater reduction in PI3K-pathway signaling associated with better PFS determined by laboratory tests and tumor assessments.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: No time limitPopulation: Data not collected
Responding tumors lack gene expression signatures of PI3K pathway activation, and progressing tumors demonstrate gene expression signatures of PI3K pathway activation - determined by laboratory tests and tumor assessments.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: No time limitPopulation: Data not collected
Responding tumors lack gene expression signatures of MAPK pathway activation, and progressing tumors demonstrate gene expression signatures of MAPK pathway activation - determined by laboratory tests and tumor assessments.
Outcome measures
Outcome data not reported
Adverse Events
Vemurafenib-Naïve
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Vemurafenib-Resistant
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vemurafenib-Naïve
n=3 participants at risk
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
Vemurafenib-Resistant
n=5 participants at risk
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Hepatobiliary disorders
Biliary Fistula
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Nervous system disorders
Seizure
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Blood and lymphatic system disorders
Renal insufficiency
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Vascular disorders
Hypotension
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
Other adverse events
| Measure |
Vemurafenib-Naïve
n=3 participants at risk
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
Vemurafenib-Resistant
n=5 participants at risk
150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
Dose Level -1:
BKM120 60 mg daily Vemurafenib 480 mg bid
Phase I, Dose Level 1:
BKM120 60 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 2:
BKM120 80 mg daily Vemurafenib 720 mg bid
Phase I, Dose Level 3:
BKM120 100 mg daily Vemurafenib 720 mg bid Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.
BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
|
|---|---|---|
|
Blood and lymphatic system disorders
elevated LDH
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Endocrine disorders
adrenal insufficiency
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Eye disorders
eye redness
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
abdominal pain
|
33.3%
1/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Gastrointestinal disorders
vomiting
|
33.3%
1/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Gastrointestinal disorders
diarrhea
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
nausea
|
33.3%
1/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Gastrointestinal disorders
Mucositis oral
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Gastrointestinal disorders
Oral Pain
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
General disorders
Fever
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
General disorders
Chills
|
33.3%
1/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
General disorders
fatigue
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
General disorders
Hypothermia
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Infections and infestations
Rash on lower abdomen
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Infections and infestations
MRSA infection
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Injury, poisoning and procedural complications
Bruising
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Investigations
weight loss
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
QtC Prolongation
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
creatinine increased
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
alkaline phosphatase increased
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
ALT increased
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
AST increased
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
Decreased wbc
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Metabolism and nutrition disorders
hypokalemia
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Metabolism and nutrition disorders
hypoglycemia
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Metabolism and nutrition disorders
hyponatremia
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Metabolism and nutrition disorders
hypoalbuminemia
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Metabolism and nutrition disorders
anorexia
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
66.7%
2/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
shoulder pain
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
33.3%
1/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Joint pain (pain in extremity)
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Nervous system disorders
fingertip numbness
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
headache
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
Restlessness
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Nervous system disorders
Tingling Extremities (Parasthesia)
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Nervous system disorders
somnolence
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
tremor
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Psychiatric disorders
anxiety
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Psychiatric disorders
depression
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Psychiatric disorders
Agitation
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Psychiatric disorders
Confusion
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Psychiatric disorders
Decreased concentration
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Renal and urinary disorders
proteinuria
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Reproductive system and breast disorders
Groin/testicular pain
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
66.7%
2/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinnorhea (Pharyngeal mucositis)
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
Rash maculopapular
|
100.0%
3/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
photosensitivity
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
alopecia
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
desquamation of hands & feet
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
Crust on elbow
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Skin and subcutaneous tissue disorders
Erythemia nodosum
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
General disorders
Decreased activity level
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Blood and lymphatic system disorders
high eosinophil count
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Blood and lymphatic system disorders
LDH increased
|
33.3%
1/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Blood and lymphatic system disorders
low hematocrit
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place