NCT01107418

Brief Summary

This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 \[RG7204; PLEXXIKON; PLX4032\] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is \<100 patients.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
52

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2010

Typical duration for phase_1

Geographic Reach
2 countries

13 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

April 12, 2010

Completed
9 days until next milestone

First Posted

Study publicly available on registry

April 21, 2010

Completed
10 days until next milestone

Study Start

First participant enrolled

May 1, 2010

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2013

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

August 26, 2015

Completed
Last Updated

August 26, 2015

Status Verified

July 1, 2015

Enrollment Period

2.8 years

First QC Date

April 12, 2010

Results QC Date

July 29, 2015

Last Update Submit

July 29, 2015

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (15)

  • Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

  • Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1

    Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1

  • Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

  • Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

  • Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

  • Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

  • Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

  • Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15

  • Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15

    Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15

  • Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15

    Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  • Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15

    Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  • Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15

    Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  • Apparent Clearance (CL/F) of Vemurafenib on Day 15

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

    Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  • Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15

    Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).

    Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  • Accumulation Ratio of Vemurafenib on Day 15

    Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.

    Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15

Secondary Outcomes (2)

  • Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)

    Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)

  • Overall Survival (OS)

    Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)

Study Arms (4)

1

EXPERIMENTAL
Drug: RO5185426

2

EXPERIMENTAL
Drug: RO5185426

3

EXPERIMENTAL
Drug: RO5185426

4

EXPERIMENTAL
Drug: RO5185426

Interventions

RO5185426DRUG

dosage b) orally twice daily, days 1-15 (morning dose)

2

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 IIIc or IV (AJCC)
  • failure of at least one prior standard of care regimen
  • positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
  • ECOG performance status 0 or 1
  • adequate hematologic, renal and liver function

You may not qualify if:

  • active CNS lesions on CT/MRI within 28 days prior to enrollment
  • history of spinal cord compression o carcinomatous meningitis
  • anticipated or ongoing anti-cancer therapies other than those administered in this study
  • previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  • severe cardiovascular disease within 6 months prior to 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Unknown Facility

La Jolla, California, 92093, United States

Location

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

Stanford, California, 94305, United States

Location

Unknown Facility

New Haven, Connecticut, 06510-3289, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Park Ridge, Illinois, 60068, United States

Location

Unknown Facility

Sioux City, Iowa, 51101, United States

Location

Unknown Facility

Omaha, Nebraska, 68114, United States

Location

Unknown Facility

Columbus, Ohio, 43219, United States

Location

Unknown Facility

East Providence, Rhode Island, 02915, United States

Location

Unknown Facility

Charlottesville, Virginia, 22908, United States

Location

Unknown Facility

Adelaide, South Australia, 5000, Australia

Location

Unknown Facility

Melbourne, Victoria, 3181, Australia

Location

Related Publications (2)

  • 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

  • Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.

    PMID: 23457002DERIVED

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

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
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 12, 2010

First Posted

April 21, 2010

Study Start

May 1, 2010

Primary Completion

February 1, 2013

Study Completion

February 1, 2013

Last Updated

August 26, 2015

Results First Posted

August 26, 2015

Record last verified: 2015-07

Locations

AU(2)US(11)