Trial Outcomes & Findings for Study to Investigate the Objective Response Rate of Dabrafenib in Combination With Trametinib in Subjects With BRAF V600 Mutation-Positive Melanoma (NCT NCT02083354)
NCT ID: NCT02083354
Last Updated: 2022-02-01
Results Overview
To determine ORR of dabrafenib in combination with trametinib in subjects with BRAF V600 mutation-positive, unresectable or metastatic melanoma. ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 and as assessed by the investigator.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
77 participants
Primary outcome timeframe
Up to 35 months
Results posted on
2022-02-01
Participant Flow
77 participants were enrolled in the study.
Participant milestones
| Measure |
Arm 1
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Overall Study
STARTED
|
77
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
64
|
Reasons for withdrawal
| Measure |
Arm 1
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Disease progression
|
46
|
|
Overall Study
Study closed/terminated
|
5
|
Baseline Characteristics
Study to Investigate the Objective Response Rate of Dabrafenib in Combination With Trametinib in Subjects With BRAF V600 Mutation-Positive Melanoma
Baseline characteristics by cohort
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Age, Continuous
|
50.6 years
STANDARD_DEVIATION 13.08 • n=5 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
77 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 35 monthsPopulation: Full Analysis Set
To determine ORR of dabrafenib in combination with trametinib in subjects with BRAF V600 mutation-positive, unresectable or metastatic melanoma. ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 and as assessed by the investigator.
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
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|---|---|
|
Objective Response Rate (ORR)
|
61 Percentage of Participants
Interval 49.2 to 72.0
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: Full analysis set
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Progression-free Survival (PFS) - Median
|
9.17 months
Interval 7.26 to 12.88
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: Full analysis set
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause. Censored, follow-up ongoing - These subjects show as ongoing in the clinical database even though no subjects are currently ongoing, as no changes to the data were permitted after 30-Jun-2019 due to local regulations in China.
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
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|---|---|
|
Progression-free Survival (PFS)
Progressive Disease (PD) (event)
|
52 Participants
|
|
Progression-free Survival (PFS)
Died (event)
|
4 Participants
|
|
Progression-free Survival (PFS)
Censored, follow-up ended
|
10 Participants
|
|
Progression-free Survival (PFS)
Censored, follow-up ongoing
|
11 Participants
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: Full analysis set, for participants who achieved CR or PR.
Duration of response is defined as the time from first documented evidence of complete response (CR) or partial response (PR) until the earliest date of documented radiological progression or death due to any cause among subjects who achieved a confirmed CR or PR.
Outcome measures
| Measure |
Arm 1
n=48 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
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|---|---|
|
Duration of Response (DOR) - Estimate for Duration of Response - Median
|
12.65 Months
Interval 5.62 to 25.23
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: Full analysis set
Duration of response is defined as the time from first documented evidence of complete response (CR) or partial response (PR) until the earliest date of documented radiological progression or death due to any cause among subjects who achieved a confirmed CR or PR. Censored, follow-up ongoing - These subjects show as ongoing in the clinical database even though no subjects are currently ongoing, as no changes to the data were permitted after 30-Jun-2019 due to local regulations in China.
Outcome measures
| Measure |
Arm 1
n=48 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
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|---|---|
|
Duration of Response (DOR)
PFS - Disease Progression
|
27 Participants
|
|
Duration of Response (DOR)
PFS - Death
|
2 Participants
|
|
Duration of Response (DOR)
PFS - Censored, follow-up ended
|
9 Participants
|
|
Duration of Response (DOR)
PFS - Censored, follow-up ongoing
|
10 Participants
|
SECONDARY outcome
Timeframe: Approximately 5 yearsPopulation: Full analysis set
OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Overall Survival (OS) - Median
|
22.90 Months
Interval 16.62 to 27.4
|
SECONDARY outcome
Timeframe: Approximately 5 yearsPopulation: Full analysis set
OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Censored, follow-up ongoing - These subjects show as ongoing in the clinical database even though no subjects are currently ongoing, as no changes to the data were permitted after 30-Jun-2019 due to local regulations in China.
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Overall Survival (OS)
Died (Event)
|
43 Participants
|
|
Overall Survival (OS)
Censored, follow-up ended
|
13 Participants
|
|
Overall Survival (OS)
Censored, follow-up ongoing
|
21 Participants
|
SECONDARY outcome
Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib).Population: Safety set
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Number of Participants With Adverse Events
Adverse events - all grades
|
76 Participants
|
|
Number of Participants With Adverse Events
Adverse events - Treatment-related - all grades
|
69 Participants
|
|
Number of Participants With Adverse Events
SAEs - all grades
|
18 Participants
|
|
Number of Participants With Adverse Events
SAEs - Treatment-related - all grades
|
9 Participants
|
|
Number of Participants With Adverse Events
Fatal SAEs - all grades
|
4 Participants
|
|
Number of Participants With Adverse Events
Fatal SAEs - Treatment-related - all grades
|
1 Participants
|
|
Number of Participants With Adverse Events
AEs leading to discontinuation - all grades
|
6 Participants
|
|
Number of Participants With Adverse Events
AEs leading to discontinuation - Treatment-related - all grades
|
3 Participants
|
|
Number of Participants With Adverse Events
AEs leading to dose adjustment/interruption - all grades
|
39 Participants
|
|
Number of Participants With Adverse Events
AEs leading to dose reduction - all grades
|
23 Participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Cmax is the maximum peak concentration.
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Dabrafenib - Cmax
Day 1
|
2950 ng/mL
Geometric Coefficient of Variation 72.8
|
|
Population Pharmacokinetics of Dabrafenib - Cmax
Day 15 (n=18)
|
2300 ng/mL
Geometric Coefficient of Variation 70.6
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Tmax is Time to Cmax (maximum peak concentration).
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Dabrafenib - Tmax
Day 1
|
1.95 hr
Interval 0.933 to 10.0
|
|
Population Pharmacokinetics of Dabrafenib - Tmax
Day 15 (n=18)
|
1.5 hr
Interval 0.5 to 3.0
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
AUC is the area under the concentration-time curve.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Dabrafenib - AUC(0-12)
Day 1
|
11400 h.ng/mL
Geometric Coefficient of Variation 46.1
|
|
Population Pharmacokinetics of Dabrafenib - AUC(0-12)
Day 15
|
6600 h.ng/mL
Geometric Coefficient of Variation 55.6
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Ctrough is trough concentration.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Dabrafenib - Ctrough
|
77 ng/mL
Geometric Coefficient of Variation 84.3
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Racc is the accumulation ratio.
Outcome measures
| Measure |
Arm 1
n=14 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Dabrafenib - Racc
|
0.624 ratio
Geometric Coefficient of Variation 42.7
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Cmax is the maximum peak concentration.
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Hydroxydabrafenib - Cmax
Day 1
|
1230 ng/mL
Geometric Coefficient of Variation 44.1
|
|
Population Pharmacokinetics of Hydroxydabrafenib - Cmax
Day 15 (n=18)
|
1200 ng/mL
Geometric Coefficient of Variation 58.7
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Tmax is Time to Cmax (maximum peak concentration).
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Hydroxydabrafenib - Tmax
Day 1
|
3.08 hr
Interval 1.45 to 10.0
|
|
Population Pharmacokinetics of Hydroxydabrafenib - Tmax
Day 15 (n=18)
|
1.96 hr
Interval 0.967 to 3.0
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
AUC is the area under the concentration-time curve.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Hydroxydabrafenib - AUC(0-12)
Day 1 (n=17)
|
7930 h.ng/mL
Geometric Coefficient of Variation 43
|
|
Population Pharmacokinetics of Hydroxydabrafenib - AUC(0-12)
Day 15
|
4440 h.ng/mL
Geometric Coefficient of Variation 43.4
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Rm/p is the metabolite-to-parent ratio.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Hydroxydabrafenib - Rm/p
Day 1 (n=17)
|
0.68 ratio
Geometric Coefficient of Variation 17
|
|
Population Pharmacokinetics of Hydroxydabrafenib - Rm/p
Day 15
|
0.653 ratio
Geometric Coefficient of Variation 21.4
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Ctrough is trough concentration.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Hydroxydabrafenib - Ctrough
|
94 ng/mL
Geometric Coefficient of Variation 61.9
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Racc is the accumulation ratio.
Outcome measures
| Measure |
Arm 1
n=13 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Hydroxydabrafenib - Racc
|
0.56 ratio
Geometric Coefficient of Variation 35.5
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Cmax is the maximum peak concentration.
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - Cmax
Day 1
|
48.9 ng/mL
Geometric Coefficient of Variation 93.5
|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - Cmax
Day 15 (n=18)
|
466 ng/mL
Geometric Coefficient of Variation 51.6
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Tmax is Time to Cmax (maximum peak concentration).
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - Tmax
Day 1
|
9.9 hr
Interval 7.92 to 10.0
|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - Tmax
Day 15 (n=18)
|
2.48 hr
Interval 0.0 to 10.1
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
AUC is the area under the concentration-time curve. AUC0-12 and Rm/p could not be calculated on Day 1 because all desmethyl-dabrafenib PK profiles on Day 1 were still ascending. Therefore, the Racc on Day 15 could not be calculated for desmethyldabrafenib.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - AUC(0-12)
|
3960 h.ng/mL
Geometric Coefficient of Variation 52.9
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Rm/p is the metabolite-to-parent ratio. AUC0-12 and Rm/p could not be calculated on Day 1 because all desmethyl-dabrafenib PK profiles on Day 1 were still ascending. Therefore, the Racc on Day 15 could not be calculated for desmethyldabrafenib.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - Rm/p
|
0.616 ratio
Geometric Coefficient of Variation 51.4
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Ctrough is trough concentration.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Desmethyl-dabrafenib - Ctrough
|
365 ng/mL
Geometric Coefficient of Variation 63.7
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Cmax is the maximum peak concentration.
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Carboxydabrafenib - Cmax
Day 15 (n=18)
|
9750 ng/mL
Geometric Coefficient of Variation 32.8
|
|
Population Pharmacokinetics of Carboxydabrafenib - Cmax
Day 1
|
3760 ng/mL
Geometric Coefficient of Variation 75.7
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Tmax is Time to Cmax (maximum peak concentration).
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Carboxydabrafenib - Tmax
Day 1
|
8.94 hr
Interval 4.0 to 10.1
|
|
Population Pharmacokinetics of Carboxydabrafenib - Tmax
Day 15 (n=18)
|
3.5 hr
Interval 2.0 to 6.08
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
AUC is the area under the concentration-time curve.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Carboxydabrafenib - AUC(0-12)
Day 1 (n=1)
|
34400 h.ng/mL
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation does not apply when n is 1
|
|
Population Pharmacokinetics of Carboxydabrafenib - AUC(0-12)
Day 15
|
86500 h.ng/mL
Geometric Coefficient of Variation 34.1
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Rm/p is the metabolite-to-parent ratio.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Carboxydabrafenib - Rm/p
Day 1 (n=1)
|
3.34 ratio
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation does not apply when n is 1
|
|
Population Pharmacokinetics of Carboxydabrafenib - Rm/p
Day 15
|
12.4 ratio
Geometric Coefficient of Variation 55.8
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Ctrough is trough concentration.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Carboxydabrafenib - Ctrough
|
5160 ng/mL
Geometric Coefficient of Variation 46
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Racc is the accumulation ratio.
Outcome measures
| Measure |
Arm 1
n=1 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Carboxydabrafenib - Racc
|
1.51 ratio
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation does not apply when n is 1
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Cmax is the maximum peak concentration.
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Trametinib - Cmax
Day 1
|
9.87 ng/mL
Geometric Coefficient of Variation 58.1
|
|
Population Pharmacokinetics of Trametinib - Cmax
Day 15 (n=18)
|
25.9 ng/mL
Geometric Coefficient of Variation 33.3
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Tmax is Time to Cmax (maximum peak concentration).
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Trametinib - Tmax
Day 1
|
1.5 hr
Interval 0.483 to 4.0
|
|
Population Pharmacokinetics of Trametinib - Tmax
Day 15 (n=18)
|
11.3 hr
Interval 6.64 to 17.0
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Area under the concentration-time curve from time zero (predose) to last time of quantifiable concentration within a subject across all treatments
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Trametinib - AUC(0-t)
Day 1
|
72.6 h.ng/mL
Geometric Coefficient of Variation 27.3
|
|
Population Pharmacokinetics of Trametinib - AUC(0-t)
Day 15 (n=18)
|
346 h.ng/mL
Geometric Coefficient of Variation 24
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
AUC is the area under the concentration-time curve.
Outcome measures
| Measure |
Arm 1
n=20 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Trametinib - AUC(0-24)
Day 1
|
72.7 h.ng/mL
Geometric Coefficient of Variation 27.2
|
|
Population Pharmacokinetics of Trametinib - AUC(0-24)
Day 15 (n=18)
|
357 h.ng/mL
Geometric Coefficient of Variation 22.7
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Ctrough is trough concentration.
Outcome measures
| Measure |
Arm 1
n=18 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Trametinib - Ctrough
|
11.2 ng/mL
Geometric Coefficient of Variation 25.2
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK analysis set
Racc is the accumulation ratio.
Outcome measures
| Measure |
Arm 1
n=15 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
Population Pharmacokinetics of Trametinib - Racc
|
5.16 ratio
Geometric Coefficient of Variation 15.1
|
POST_HOC outcome
Timeframe: The collection period for mortality data occurred from start of treatment until the end of the post-treatment period, up to a maximum timeframe of 4.25 years.Population: Safety Set (on-treatment deaths) and Full Analysis Set (total deaths)
Deaths are reported in the following categories: On-treatment deaths are defined as deaths that occurred after treatment start up to 30 days after study drug discontinuation. Post-treatment deaths are defined as deaths that occurred more than 30 days after study drug discontinuation until end of post-treatment follow up. Total deaths are the combination of on-treatment deaths and post-treatment deaths.
Outcome measures
| Measure |
Arm 1
n=77 Participants
All subjects received the combination of dabrafenib (150 mg) and trametinib (2 mg) in the morning at approximately the same time every day. The second dose of dabrafenib (150 mg) alone was to be administered approximately 12 hours after the morning dose. Subjects were to continue study treatment until disease progression, death, unacceptable toxicity, withdrawal of consent, or study closure
|
|---|---|
|
All Collected Deaths
Total Deaths
|
43 Participants
|
|
All Collected Deaths
On-treatment Deaths
|
16 Participants
|
|
All Collected Deaths
Post-treatment Deaths
|
27 Participants
|
Adverse Events
All Patients
Serious events: 18 serious events
Other events: 75 other events
Deaths: 16 deaths
Serious adverse events
| Measure |
All Patients
n=77 participants at risk
All Patients
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Eye disorders
Uveitis
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Pyrexia
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Hepatobiliary disorders
Acute hepatic failure
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Hepatobiliary disorders
Liver injury
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Arthritis infective
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Cellulitis
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Chikungunya virus infection
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Diarrhoea infectious
|
2.6%
2/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Infection
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Pneumonia
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Post procedural sepsis
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Pyelonephritis acute
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Septic shock
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Skin infection
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Soft tissue infection
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Ejection fraction decreased
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
White blood cell count decreased
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Psychiatric disorders
Confusional state
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Reproductive system and breast disorders
Uterine polyp
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
1.3%
1/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
Other adverse events
| Measure |
All Patients
n=77 participants at risk
All Patients
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
48.1%
37/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Abdominal distension
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Constipation
|
16.9%
13/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Diarrhoea
|
13.0%
10/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Nausea
|
28.6%
22/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Gastrointestinal disorders
Vomiting
|
23.4%
18/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Asthenia
|
6.5%
5/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Chest discomfort
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Chest pain
|
6.5%
5/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Chills
|
19.5%
15/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Fatigue
|
9.1%
7/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Malaise
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Oedema peripheral
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
General disorders
Pyrexia
|
59.7%
46/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Cystitis
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Infections and infestations
Nasopharyngitis
|
28.6%
22/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Alanine aminotransferase increased
|
24.7%
19/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Aspartate aminotransferase increased
|
31.2%
24/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Blood alkaline phosphatase increased
|
26.0%
20/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Blood lactate dehydrogenase increased
|
27.3%
21/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Gamma-glutamyltransferase increased
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Neutrophil count decreased
|
37.7%
29/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Platelet count decreased
|
20.8%
16/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Weight decreased
|
13.0%
10/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
Weight increased
|
22.1%
17/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Investigations
White blood cell count decreased
|
45.5%
35/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.6%
12/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
41.6%
32/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.5%
5/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
6.5%
5/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
7/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
6.5%
5/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
7/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
11/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.1%
7/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Nervous system disorders
Dizziness
|
24.7%
19/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Nervous system disorders
Headache
|
16.9%
13/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Psychiatric disorders
Insomnia
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.4%
18/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Skin and subcutaneous tissue disorders
Panniculitis
|
6.5%
5/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.8%
6/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Skin and subcutaneous tissue disorders
Rash
|
37.7%
29/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
5.2%
4/77 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 51 months (for both dabrafenib and also Rametinib) (approx 4.25 years).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER