TriangleNCT02124772 · OUTCOME
Maximum Observed Plasma Concentration (Cmax) of Trametinib When Administered Alone and in Combination With Dabrafenib
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- GEOMETRIC_MEAN
- Unit
- ng/mL
- Interval / dispersion
- Geometric Coefficient of Variation
- Time frame
- pre dose, 1, 2, 4, 7, 10 and 24 hours post trametinib dose on Cycle 1 Day 15 (part A and B) and pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post trametinib dose on Cycle 1 Day 15 (part C and D). The duration of 1 cycle was 28 days.
What was measured
Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Analysis population: All subjects who received at least one dose of trametinib in Part A, B, C and D and provided an evaluable PK profile with a value for the outcome measure
Groups in this outcome
Part A - TMT 0.0125 mg/kg/Day
Participants treated with trametinib 0.0125 mg/kg/day
Part A - TMT 0.025 mg/kg/Day
Participants treated with trametinib 0.025 mg/kg/day
Part A - TMT 0.032 mg/kg/Day
Participants under 6 years of age treated with trametinib 0.032 mg/kg/day
Part A - TMT 0.04 mg/kg/Day
Participants treated with trametinib 0.04 mg/kg/day
Part B - Neuroblastoma
Participants with refractory or relapsed neuroblastoma treated with trametinib 0.025 mg/kg/day
Part B - LGG Fusion
Participants with recurrent or unresectable low grade glioma (LGG) with BRAF tandem duplication with fusion treated with trametinib 0.025 mg/kg/day
Part B - NF-1 With PN
Participants with neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) treated with trametinib 0.025 mg/kg/day
Part B - BRAF V600 Mutant Solid Tumor
Participants with BRAF V600 mutant solid tumors treated with trametinib 0.025 mg/kg/day
Part B - All Tumor Types TMT 0.025 mg/kg/Day
Participants (all tumor types in Part B) treated with trametinib 0.025 mg/kg/day
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D
Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects)
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D
Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D
Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
Part D - LGG
Participants with low grade glioma (LGG) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
Part D - LCH
Participants with Langerhans cell histiocytosis (LCH) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D
Participants under 6 years of age (all tumor types in Part D) treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D
Participants (all tumor types in Part D) treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
| Group | Source count |
|---|---|
| Part A - TMT 0.0125 mg/kg/Day | 3 |
| Part A - TMT 0.025 mg/kg/Day | 18 |
| Part A - TMT 0.032 mg/kg/Day | 9 |
| Part A - TMT 0.04 mg/kg/Day | 16 |
| Part B - Neuroblastoma | 9 |
| Part B - LGG Fusion | 10 |
| Part B - NF-1 With PN | 10 |
| Part B - BRAF V600 Mutant Solid Tumor | 9 |
| Part B - All Tumor Types TMT 0.025 mg/kg/Day | 38 |
| Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D | 1 |
| Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D | 1 |
| Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D | 6 |
| Part D - LGG | 20 |
| Part D - LCH | 6 |
| Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D | 5 |
| Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D | 21 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Part A - TMT 0.0125 mg/kg/Day | 9.61 | 32.9 | Not reported | Not reported | Not reported |
| Part A - TMT 0.025 mg/kg/Day | 21.1 | 33.3 | Not reported | Not reported | Not reported |
| Part A - TMT 0.032 mg/kg/Day | 26.1 | 16.8 | Not reported | Not reported | Not reported |
| Part A - TMT 0.04 mg/kg/Day | 32.6 | 28.9 | Not reported | Not reported | Not reported |
| Part B - Neuroblastoma | 26.6 | 39.6 | Not reported | Not reported | Not reported |
| Part B - LGG Fusion | 22.1 | 41.9 | Not reported | Not reported | Not reported |
| Part B - NF-1 With PN | 21.6 | 26.1 | Not reported | Not reported | Not reported |
| Part B - BRAF V600 Mutant Solid Tumor | 27.5 | 31.6 | Not reported | Not reported | Not reported |
| Part B - All Tumor Types TMT 0.025 mg/kg/Day | 24.2 | 35.6 | Not reported | Not reported | Not reported |
| Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D | 26.0 | Not reported | Not reported | Not reported | Not reported |
| Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D | 24.5 | Not reported | Not reported | Not reported | Not reported |
| Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D | 23.7 | 36.3 | Not reported | Not reported | Not reported |
| Part D - LGG | 22.9 | 29.2 | Not reported | Not reported | Not reported |
| Part D - LCH | 15.6 | 52.5 | Not reported | Not reported | Not reported |
| Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D | 25.9 | 35.8 | Not reported | Not reported | Not reported |
| Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D | 20.0 | 38.1 | Not reported | Not reported | Not reported |
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 32.9
- value
- 9.61
- group Id
- OG001
- spread
- 33.3
- value
- 21.1
- group Id
- OG002
- spread
- 16.8
- value
- 26.1
- group Id
- OG003
- spread
- 28.9
- value
- 32.6
- group Id
- OG004
- spread
- 39.6
- value
- 26.6
- group Id
- OG005
- spread
- 41.9
- value
- 22.1
- group Id
- OG006
- spread
- 26.1
- value
- 21.6
- group Id
- OG007
- spread
- 31.6
- value
- 27.5
- group Id
- OG008
- spread
- 35.6
- value
- 24.2
- group Id
- OG009
- value
- 26.0
- group Id
- OG010
- value
- 24.5
- group Id
- OG011
- spread
- 36.3
- value
- 23.7
- denoms
- counts
- group Id
- OG000
- value
- 3
- group Id
- OG001
- value
- 18
- group Id
- OG002
- value
- 9
- group Id
- OG003
- value
- 16
- group Id
- OG004
- value
- 9
- group Id
- OG005
- value
- 10
- group Id
- OG006
- value
- 10
- group Id
- OG007
- value
- 9
- group Id
- OG008
- value
- 38
- group Id
- OG009
- value
- 1
- group Id
- OG010
- value
- 1
- group Id
- OG011
- value
- 6
- units
- Participants
- description
- Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
- dispersion Type
- Geometric Coefficient of Variation
- groups
- description
- Participants treated with trametinib 0.0125 mg/kg/day
- id
- OG000
- title
- Part A - TMT 0.0125 mg/kg/Day
- description
- Participants treated with trametinib 0.025 mg/kg/day
- id
- OG001
- title
- Part A - TMT 0.025 mg/kg/Day
- description
- Participants under 6 years of age treated with trametinib 0.032 mg/kg/day
- id
- OG002
- title
- Part A - TMT 0.032 mg/kg/Day
- description
- Participants treated with trametinib 0.04 mg/kg/day
- id
- OG003
- title
- Part A - TMT 0.04 mg/kg/Day
- description
- Participants with refractory or relapsed neuroblastoma treated with trametinib 0.025 mg/kg/day
- id
- OG004
- title
- Part B - Neuroblastoma
- description
- Participants with recurrent or unresectable low grade glioma (LGG) with BRAF tandem duplication with fusion treated with trametinib 0.025 mg/kg/day
- id
- OG005
- title
- Part B - LGG Fusion
- description
- Participants with neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) treated with trametinib 0.025 mg/kg/day
- id
- OG006
- title
- Part B - NF-1 With PN
- description
- Participants with BRAF V600 mutant solid tumors treated with trametinib 0.025 mg/kg/day
- id
- OG007
- title
- Part B - BRAF V600 Mutant Solid Tumor
- description
- Participants (all tumor types in Part B) treated with trametinib 0.025 mg/kg/day
- id
- OG008
- title
- Part B - All Tumor Types TMT 0.025 mg/kg/Day
- description
- Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects)
- id
- OG009
- title
- Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D
- description
- Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
- id
- OG010
- title
- Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D
- description
- Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
- id
- OG011
- title
- Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D
- param Type
- GEOMETRIC_MEAN
- population Description
- All subjects who received at least one dose of trametinib in Part A, B, C and D and provided an evaluable PK profile with a value for the outcome measure
- reporting Status
- POSTED
- time Frame
- pre dose, 1, 2, 4, 7, 10 and 24 hours post trametinib dose on Cycle 1 Day 15 (part A and B) and pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post trametinib dose on Cycle 1 Day 15 (part C and D). The duration of 1 cycle was 28 days.
- title
- Maximum Observed Plasma Concentration (Cmax) of Trametinib When Administered Alone and in Combination With Dabrafenib
- type
- SECONDARY
- unit Of Measure
- ng/mL
Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0
Preserved source evidence · Independent clinical review pending · Not medical advice