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NCT02124772 · OUTCOME

Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady-state (AUCtau) of Dabrafenib When Administered in Combination With Trametinib

Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations · Source last updated 2021-07-14

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
GEOMETRIC_MEAN
Unit
hours*ng/mL
Interval / dispersion
Geometric Coefficient of Variation
Time frame
pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post dabrafenib dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.

What was measured

Pharmacokinetic (PK) parameters were calculated based on dabrafenib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for area under the curve calculation. The duration of the dosing interval (tau) was 12 hours for dabrafenib.

Analysis population: All subjects who received at least one dose of dabrafenib in Part C and D and provided an evaluable PK profile with a value for the outcome measure

Groups in this outcome

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 identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D3
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D7
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D6
Part D - LGG19
Part D - LCH8
Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D6
Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D21

Reported measurements

Source class 1
Values in hours*ng/mL · Interval/dispersion: Geometric Coefficient of Variation
GroupValueSpreadLowerUpperComment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D2870116.6Not reportedNot reportedNot reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D416024.6Not reportedNot reportedNot reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D404047.9Not reportedNot reportedNot reported
Part D - LGG407046.7Not reportedNot reportedNot reported
Part D - LCH391037.4Not reportedNot reportedNot reported
Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D415030.2Not reportedNot reportedNot reported
Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D399047.3Not reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        spread
        116.6
        value
        2870
      2. group Id
        OG001
        spread
        24.6
        value
        4160
      3. group Id
        OG002
        spread
        47.9
        value
        4040
      4. group Id
        OG003
        spread
        46.7
        value
        4070
      5. group Id
        OG004
        spread
        37.4
        value
        3910
      6. group Id
        OG005
        spread
        30.2
        value
        4150
      7. group Id
        OG006
        spread
        47.3
        value
        3990
denoms
  1. counts
    1. group Id
      OG000
      value
      3
    2. group Id
      OG001
      value
      7
    3. group Id
      OG002
      value
      6
    4. group Id
      OG003
      value
      19
    5. group Id
      OG004
      value
      8
    6. group Id
      OG005
      value
      6
    7. group Id
      OG006
      value
      21
    units
    Participants
description
Pharmacokinetic (PK) parameters were calculated based on dabrafenib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for area under the curve calculation. The duration of the dosing interval (tau) was 12 hours for dabrafenib.
dispersion Type
Geometric Coefficient of Variation
groups
  1. 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
    OG000
    title
    Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D
  2. 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
    OG001
    title
    Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D
  3. 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
    OG002
    title
    Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D
  4. description
    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)
    id
    OG003
    title
    Part D - LGG
  5. description
    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)
    id
    OG004
    title
    Part D - LCH
  6. description
    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)
    id
    OG005
    title
    Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D
  7. description
    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)
    id
    OG006
    title
    Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D
param Type
GEOMETRIC_MEAN
population Description
All subjects who received at least one dose of dabrafenib in Part C and D and provided an evaluable PK profile with a value for the outcome measure
reporting Status
POSTED
time Frame
pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post dabrafenib dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.
title
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady-state (AUCtau) of Dabrafenib When Administered in Combination With Trametinib
type
SECONDARY
unit Of Measure
hours*ng/mL

Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0

Preserved source evidence · Independent clinical review pending · Not medical advice