Clinical Trials/NCT01264380

NCT01264380

Completed

Phase 1

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

Hoffmann-La Roche0 sites16 target enrollmentJanuary 2011

ConditionsMalignant Melanoma

InterventionsRO5185426

DrugsRO5185426

Overview

Phase: Phase 1
Intervention: RO5185426
Conditions: Malignant Melanoma
Sponsor: Hoffmann-La Roche
Enrollment: 16
Primary Endpoint: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

January 2011

End Date

May 2013

Last Updated

9 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Adult patients, \>/= 18 years of age
•Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
•Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
•Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be \>/= 28 days; patients must have recovered fully from toxicities of all prior therapy
•Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
•Evaluable disease (measurable for disease progression according to RECIST criteria)
•Adequate hematological, renal and liver function

Exclusion Criteria

•Active CNS lesions
•History of or known spinal cord compression or carcinomatous meningitis
•Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
•Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix
•Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
•Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug

Arms & Interventions

1

Intervention: RO5185426

2

Intervention: RO5185426

C

Intervention: RO5185426

Outcomes

Primary Outcomes

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

Time Frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

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

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

Time Frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

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

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

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

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

Time Frame: Pre-dose on Periods A and B

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.

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

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

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

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) in the Fasted and Fed States

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.

Secondary Outcomes

Overall Survival (OS)(From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124))
Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)(From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124))