TriangleNCT02124772 · OUTCOME
Apparent Plasma Clearance (CL/F) 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
- mL/hour
- 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. Apparent plasma clearance (CL/F) values were calculated as Dose/AUCtau.
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 | 15 |
| 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 | 2750 | 69.4 | Not reported | Not reported | Not reported |
| Part A - TMT 0.025 mg/kg/Day | 1530 | 64.5 | Not reported | Not reported | Not reported |
| Part A - TMT 0.032 mg/kg/Day | 1240 | 25.5 | Not reported | Not reported | Not reported |
| Part A - TMT 0.04 mg/kg/Day | 2040 | 71.5 | Not reported | Not reported | Not reported |
| Part B - Neuroblastoma | 1710 | 55.6 | Not reported | Not reported | Not reported |
| Part B - LGG Fusion | 1910 | 47.8 | Not reported | Not reported | Not reported |
| Part B - NF-1 With PN | 1590 | 65.3 | Not reported | Not reported | Not reported |
| Part B - BRAF V600 Mutant Solid Tumor | 1820 | 42.6 | Not reported | Not reported | Not reported |
| Part B - All Tumor Types TMT 0.025 mg/kg/Day | 1750 | 51.5 | Not reported | Not reported | Not reported |
| Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D | 2590 | Not reported | Not reported | Not reported | Not reported |
| Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D | 3770 | Not reported | Not reported | Not reported | Not reported |
| Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D | 2010 | 38.5 | Not reported | Not reported | Not reported |
| Part D - LGG | 3540 | 54.0 | Not reported | Not reported | Not reported |
| Part D - LCH | 3060 | 44.9 | Not reported | Not reported | Not reported |
| Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D | 2180 | 23.9 | Not reported | Not reported | Not reported |
| Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D | 3810 | 49.6 | Not reported | Not reported | Not reported |
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 69.4
- value
- 2750
- group Id
- OG001
- spread
- 64.5
- value
- 1530
- group Id
- OG002
- spread
- 25.5
- value
- 1240
- group Id
- OG003
- spread
- 71.5
- value
- 2040
- group Id
- OG004
- spread
- 55.6
- value
- 1710
- group Id
- OG005
- spread
- 47.8
- value
- 1910
- group Id
- OG006
- spread
- 65.3
- value
- 1590
- group Id
- OG007
- spread
- 42.6
- value
- 1820
- group Id
- OG008
- spread
- 51.5
- value
- 1750
- group Id
- OG009
- value
- 2590
- group Id
- OG010
- value
- 3770
- group Id
- OG011
- spread
- 38.5
- value
- 2010
- denoms
- counts
- group Id
- OG000
- value
- 3
- group Id
- OG001
- value
- 18
- group Id
- OG002
- value
- 9
- group Id
- OG003
- value
- 15
- 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. Apparent plasma clearance (CL/F) values were calculated as Dose/AUCtau.
- 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
- Apparent Plasma Clearance (CL/F) of Trametinib When Administered Alone and in Combination With Dabrafenib
- type
- SECONDARY
- unit Of Measure
- mL/hour
Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0
Preserved source evidence · Independent clinical review pending · Not medical advice