NCT01264380

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2011

Typical duration for phase_1

Geographic Reach
1 country

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 20, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 21, 2010

Completed
11 days until next milestone

Study Start

First participant enrolled

January 1, 2011

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

December 17, 2015

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

2.3 years

First QC Date

December 20, 2010

Results QC Date

July 29, 2015

Last Update Submit

November 1, 2016

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (7)

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

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

    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

  • 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

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

    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

  • 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.

    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

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

    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.

    Pre-dose on Periods A and B

  • 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.

    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

  • 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.

    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

  • 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.

    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

Secondary Outcomes (2)

  • 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)

  • 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)

Study Arms (3)

1

EXPERIMENTAL
Drug: RO5185426

2

EXPERIMENTAL
Drug: RO5185426

C

EXPERIMENTAL
Drug: RO5185426

Interventions

RO5185426DRUG

Single oral dose, fasted

1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Unknown Facility

La Jolla, California, 92037, United States

Location

Unknown Facility

Los Angeles, California, 90095-1752, United States

Location

Unknown Facility

San Francisco, California, 94115-1705, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Indianapolis, Indiana, 46202, United States

Location

Unknown Facility

Iowa City, Iowa, 52242, United States

Location

Unknown Facility

Lebanon, New Hampshire, 03756, United States

Location

Unknown Facility

Charleston, South Carolina, 29425, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

Unknown Facility

Dallas, Texas, 75246, United States

Location

Related Publications (1)

  • Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.

    PMID: 24983357DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Limitations and Caveats

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

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche
genentech@druginfo.com
800-821-8590

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 20, 2010

First Posted

December 21, 2010

Study Start

January 1, 2011

Primary Completion

May 1, 2013

Study Completion

May 1, 2013

Last Updated

November 2, 2016

Results First Posted

December 17, 2015

Record last verified: 2016-11

Locations

US(10)