Trial · NCT02124772

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

NCT02124772, Phase 1, Phase 2, Completed, Novartis Pharmaceuticals; results first posted 2021-07-14

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. 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. Trials, record NCT02124772. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02124772

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: 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
NCT number: NCT02124772
Status: Completed
Phases: Phase 1, Phase 2
Enrollment: 139 participants, actual
Lead sponsor: Novartis Pharmaceuticals
Conditions: Cancer
Interventions: Trametinib, Dabrafenib
First posted: 2014-04-28
Last updated: 2021-07-14
Other registries' IDs: eudract:2013-003596-35
Results first posted: 2021-07-14

Source ClinicalTrials.gov

Registered outcomes26

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	From the day of the first dose of trametinib up to 30 days after the last dose, up to maximum duration of 64 months	Incidence of treatment emergent adverse events is defined as number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. The number of participants in each category is reported in the table.
Primary	Average Steady State Plasma Concentration (Cavg) of Trametinib When Administered Alone (Monotherapy)	pre dose, 1, 2, 4, 7, 10 and 24 hours post trametinib dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.	Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. The average steady state plasma concentration (Cavg) of trametinib was calculated as the ratio of area under the curve (AUC)/tau, where tau = 24 h for trametinib.
Secondary	Trough Concentration (Ctrough) of Trametinib When Administered Alone and in Combination With Dabrafenib	pre dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.	Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. Ctrough is defined as the observed plasma concentration just prior to the beginning of, or at the end, of a dosing interval.
Secondary	Maximum Observed Plasma Concentration (Cmax) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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.
Secondary	Time to Reach Maximum Plasma Concentration (Tmax) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose.
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for area under the curve calculation.
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady-state (AUCtau) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	Pharmacokinetic (PK) parameters were calculated based on trametinib 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 24 hours for trametinib.
Secondary	Apparent Plasma Clearance (CL/F) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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.
Secondary	Average Steady State Plasma Concentration (Cavg) of Trametinib When Administered in Combination With Dabrafenib	pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post trametinib dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.	Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. The average steady state plasma concentration (Cavg) of trametinib was calculated as the ratio of area under the curve (AUC)/tau, where tau = 24 h for trametinib.
Secondary	Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib in Combination With Dabrafenib	From the day of the first dose of the combination up to 30 days after the last dose, up to maximum duration of 53 months	Incidence of treatment emergent adverse events is defined as number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. The number of participants in each category is reported in the table.

1 to 10 of 26Source ClinicalTrials.gov

See all 26 registered outcomes

Outcomes26

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	From the day of the first dose of trametinib up to 30 days after the last dose, up to maximum duration of 64 months	All subjects who received at least one dose of trametinib in Part A and B	Participants	COUNT_OF_PARTICIPANTS
PRIMARY	Average Steady State Plasma Concentration (Cavg) of Trametinib When Administered Alone (Monotherapy)	pre dose, 1, 2, 4, 7, 10 and 24 hours post trametinib dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.	All subjects who received at least one dose of trametinib in Part A and B and provided an evaluable PK profile with a value for the outcome measure	ng/mL	GEOMETRIC_MEAN
SECONDARY	Trough Concentration (Ctrough) of Trametinib When Administered Alone and in Combination With Dabrafenib	pre dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.	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	ng/mL	GEOMETRIC_MEAN
SECONDARY	Maximum Observed Plasma Concentration (Cmax) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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	ng/mL	GEOMETRIC_MEAN
SECONDARY	Time to Reach Maximum Plasma Concentration (Tmax) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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	hours	MEDIAN
SECONDARY	Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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	hours*ng/mL	GEOMETRIC_MEAN
SECONDARY	Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady-state (AUCtau) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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	hours*ng/mL	GEOMETRIC_MEAN
SECONDARY	Apparent Plasma Clearance (CL/F) of Trametinib When Administered Alone and in Combination With Dabrafenib	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.	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	mL/hour	GEOMETRIC_MEAN
SECONDARY	Average Steady State Plasma Concentration (Cavg) of Trametinib When Administered in Combination With Dabrafenib	pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post trametinib dose on Cycle 1 Day 15. The duration of 1 cycle was 28 days.	All subjects who received at least one dose of trametinib in Part C and D and provided an evaluable PK profile with a value for the outcome measure	ng/mL	GEOMETRIC_MEAN
SECONDARY	Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib in Combination With Dabrafenib	From the day of the first dose of the combination up to 30 days after the last dose, up to maximum duration of 53 months	All subjects who received at least one dose of any component of the combination in Part C and Part D	Participants	COUNT_OF_PARTICIPANTS

1 to 10 of 26Source ClinicalTrials.gov

See all 26 outcomes

Results by group601

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Units
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part A - TMT 0.0125 mg/kg/Day	AEs	3	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part A - TMT 0.025 mg/kg/Day	AEs	19	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part A - TMT 0.032 mg/kg/Day	AEs	12	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part A - TMT 0.04 mg/kg/Day	AEs	16	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part B - Neuroblastoma	AEs	11	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part B - LGG Fusion	AEs	10	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part B - NF-1 With PN	AEs	10	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part B - BRAF V600 Mutant Solid Tumor	AEs	10	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part A - TMT 0.0125 mg/kg/Day	Treatment-related AEs	3	Participants
Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib Monotherapy	Part A - TMT 0.025 mg/kg/Day	Treatment-related AEs	19	Participants

1 to 10 of 601Source ClinicalTrials.gov

See all 601 results by group

Participant flow39

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Part A - TMT 0.0125 mg/kg/Day	3
Overall Study	STARTED	Part A - TMT 0.025 mg/kg/Day	19
Overall Study	STARTED	Part A - TMT 0.032 mg/kg/Day	12
Overall Study	STARTED	Part A - TMT 0.04 mg/kg/Day	16
Overall Study	STARTED	Part B - Neuroblastoma	11
Overall Study	STARTED	Part B - LGG Fusion	10
Overall Study	STARTED	Part B - NF-1 With PN	10
Overall Study	STARTED	Part B - BRAF V600 Mutant Solid Tumor	10
Overall Study	STARTED	Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	3
Overall Study	STARTED	Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	9

1 to 10 of 39Source ClinicalTrials.gov

See all 39 participant flow

Adverse events8,138

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Anaemia	Blood and lymphatic system disorders	Part A - TMT 0.0125 mg/kg/Day	0	3
other	Anaemia	Blood and lymphatic system disorders	Part A - TMT 0.025 mg/kg/Day	9	19
other	Anaemia	Blood and lymphatic system disorders	Part A - TMT 0.032 mg/kg/Day	6	12
other	Anaemia	Blood and lymphatic system disorders	Part A - TMT 0.04 mg/kg/Day	7	16
other	Anaemia	Blood and lymphatic system disorders	Part B - Neuroblastoma	6	11
other	Anaemia	Blood and lymphatic system disorders	Part B - LGG Fusion	3	10
other	Anaemia	Blood and lymphatic system disorders	Part B - NF-1 With PN	4	10
other	Anaemia	Blood and lymphatic system disorders	Part B - BRAF V600 Mutant Solid Tumor	5	10
other	Anaemia	Blood and lymphatic system disorders	Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	0	3
other	Anaemia	Blood and lymphatic system disorders	Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	4	9

1 to 10 of 8,138Source ClinicalTrials.gov

See all 8,138 adverse events

Adverse event totals39

The totals the trial posted for each group.

Total	Group	At risk
Total, all-cause mortality	Part A - TMT 0.0125 mg/kg/Day	3
Total, all-cause mortality	Part A - TMT 0.025 mg/kg/Day	19
Total, all-cause mortality	Part A - TMT 0.032 mg/kg/Day	12
Total, all-cause mortality	Part A - TMT 0.04 mg/kg/Day	16
Total, all-cause mortality	Part B - Neuroblastoma	11
Total, all-cause mortality	Part B - LGG Fusion	10
Total, all-cause mortality	Part B - NF-1 With PN	10
Total, all-cause mortality	Part B - BRAF V600 Mutant Solid Tumor	10
Total, all-cause mortality	Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	3
Total, all-cause mortality	Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	9

1 to 10 of 39Source ClinicalTrials.gov

See all 39 adverse event totals

Papers3

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
34331515	DERIVED	PubMed
36375115	DERIVED	PubMed
36884302	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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