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A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01107418
First received: April 12, 2010
Last updated: July 29, 2015
Last verified: July 2015
April 12, 2010
July 29, 2015
May 2010
February 2013   (Final data collection date for primary outcome measure)
  • Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1 [ Time Frame: 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 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1 ]
  • Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 ]
  • Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose 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.
  • Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose 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).
  • Accumulation Ratio of Vemurafenib on Day 15 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15 ]
    Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.
Pharmacokinetics: RO5185426 plasma concentration [ Time Frame: multiple sampling days 1, 2, 9, 11, 15, 16 and 18; and on day 1 cycles 1-8 and every other cycle starting cycle 9 ]
Complete list of historical versions of study NCT01107418 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: 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) ]
    Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.
  • Overall Survival (OS) [ Time Frame: 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) ]
    OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death.
  • Safety and tolerability: Incidence of adverse events (AEs) [ Time Frame: throughout study ]
  • Safety and tolerability: Assessment of routine laboratory values [ Time Frame: laboratory assessments every 3 weeks ]
  • Efficacy: Best overall response (OR) [ Time Frame: tumor assessments every 2 cycles ]
  • Efficacy: Overall survival (OS) [ Time Frame: event driven, assessed at study completion ]
Not Provided
Not Provided
 
A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
A Phase I, Randomized, Open-label, Multi-center, Multiple Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO5185426 Administered as 240 mg Tablets to Previously Treated BRAF V600E Positive Metastatic Melanoma Patients
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Melanoma
  • Drug: RO5185426
    dosage b) orally twice daily, days 1-15 (morning dose)
  • Drug: RO5185426
    dosage c) orally twice daily, days 1-15 (morning dose)
  • Drug: RO5185426
    dosage d) orally twice daily, days 1-15 (morning dose)
  • Drug: RO5185426
    960 mg orally twice daily, from day 22 onward
  • Drug: RO5185426
    dosage a) orally twice daily, days 1-15 (morning dose)
  • Experimental: 1
    Interventions:
    • Drug: RO5185426
    • Drug: RO5185426
  • Experimental: 2
    Interventions:
    • Drug: RO5185426
    • Drug: RO5185426
  • Experimental: 3
    Interventions:
    • Drug: RO5185426
    • Drug: RO5185426
  • Experimental: 4
    Interventions:
    • Drug: RO5185426
    • Drug: RO5185426

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
February 2013
February 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   United States
 
 
NCT01107418
NP25163
Not Provided
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP