Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

RO5185426

Continuous administration, orally twice daily

Clinical Trials

This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.

A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients

Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than \[\<\] 10 millimeter \[mm\] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.

Hoffmann-La Roche

Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).

Vemurafenib (RO5185426): Fasted

Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Vemurafenib (RO5185426): Fed

Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).

Vemurafenib (RO5185426)

Included all participants who received single oral dose of vemurafenib tablet at 960 mg in fasted condition first and fed condition first in Period A and Period B and twice daily dose of vemurafenib tablet at 960 mg in Period C.

All Participants

Age, Continuous

Gender

All participants who received at least 1 dose of vemurafenib.

Results for OS was not reported due to change in planned analysis.

Medical Communications

The point estimate and 90 percent (%) confidence interval (CI) of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.

Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).

Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

PK analysis population included participants who received both single doses of vemurafenib in Periods A and B without protocol violation and provided adequate PK assessments to calculate important PK parameters. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States

The point estimate and 90% CI of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.

PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States

The point estimate and 90% CI of vemurafenib plasma Cmax geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.

Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States

Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States

Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States

Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States

Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States

Intent-to-treat (ITT) population included participants with measurable disease who received at least 1 dose of vemurafenib. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)

Data for OS was not collected as there was a change in planned analysis, not to collect the data.

Overall Survival (OS)

Single oral dose of vemurafenib tablet at 960 milligrams (mg) on Day 1 was administered to participants in fasted condition (Period A \[Day 1 to Day 10\]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fed condition (Period B \[Day 11 to Day 20\]). A washout period of 10 days was maintained between Period A and B.

Vemurafenib (RO5185426): Fasted Then Fed

Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition (Period A \[Day 1 to Day 10\]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fasted condition Period B \[Day 11 to Day 20\]). A washout period of 10 days was maintained between Period A and B.

Spots Global Cancer Trial Database for A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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