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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01107418
Registration number
NCT01107418
Ethics application status
Date submitted
12/04/2010
Date registered
21/04/2010
Date last updated
26/08/2015
Titles & IDs
Public title
A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
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Scientific title
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
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Secondary ID [1]
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NP25163
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - RO5185426
Treatment: Drugs - RO5185426
Treatment: Drugs - RO5185426
Treatment: Drugs - RO5185426
Treatment: Drugs - RO5185426
Experimental: 1 -
Experimental: 2 -
Experimental: 3 -
Experimental: 4 -
Treatment: Drugs: RO5185426
dosage b) orally twice daily, days 1-15 (morning dose)
Treatment: Drugs: RO5185426
dosage c) orally twice daily, days 1-15 (morning dose)
Treatment: Drugs: RO5185426
dosage d) orally twice daily, days 1-15 (morning dose)
Treatment: Drugs: RO5185426
960 mg orally twice daily, from day 22 onward
Treatment: Drugs: RO5185426
dosage a) orally twice daily, days 1-15 (morning dose)
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1
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Assessment method [1]
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Timepoint [1]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
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Primary outcome [2]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1
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Assessment method [2]
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Timepoint [2]
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Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1
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Primary outcome [3]
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Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1
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Assessment method [3]
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Timepoint [3]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
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Primary outcome [4]
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Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1
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Assessment method [4]
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Timepoint [4]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
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Primary outcome [5]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
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Assessment method [5]
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Timepoint [5]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
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Primary outcome [6]
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Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9
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Assessment method [6]
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Timepoint [6]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
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Primary outcome [7]
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Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9
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Assessment method [7]
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Timepoint [7]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
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Primary outcome [8]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15
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Assessment method [8]
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Timepoint [8]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15
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Primary outcome [9]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15
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Assessment method [9]
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Timepoint [9]
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Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15
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Primary outcome [10]
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Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15
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Assessment method [10]
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Timepoint [10]
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Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
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Primary outcome [11]
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Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15
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Assessment method [11]
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Timepoint [11]
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Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
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Primary outcome [12]
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Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15
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Assessment method [12]
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Timepoint [12]
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Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
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Primary outcome [13]
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Apparent Clearance (CL/F) of Vemurafenib on Day 15
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Assessment method [13]
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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.
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Timepoint [13]
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Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
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Primary outcome [14]
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Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15
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Assessment method [14]
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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).
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Timepoint [14]
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Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
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Primary outcome [15]
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Accumulation Ratio of Vemurafenib on Day 15
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Assessment method [15]
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Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.
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Timepoint [15]
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Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15
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Secondary outcome [1]
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Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)
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Assessment method [1]
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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.
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Timepoint [1]
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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)
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Secondary outcome [2]
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Overall Survival (OS)
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Assessment method [2]
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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.
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Timepoint [2]
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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)
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/05/2010
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/02/2013
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Sample size
Target
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Accrual to date
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Final
52
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Recruitment in Australia
Recruitment state(s)
SA,VIC
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Recruitment hospital [1]
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- Adelaide
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Recruitment hospital [2]
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- Melbourne
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Recruitment postcode(s) [1]
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5000 - Adelaide
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Recruitment postcode(s) [2]
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3181 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Connecticut
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Country [3]
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United States of America
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State/province [3]
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Illinois
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Country [4]
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United States of America
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State/province [4]
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Iowa
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Country [5]
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United States of America
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State/province [5]
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Nebraska
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Country [6]
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United States of America
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State/province [6]
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Ohio
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Country [7]
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United States of America
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State/province [7]
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Rhode Island
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Country [8]
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United States of America
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State/province [8]
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Virginia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT01107418
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Trial related presentations / publications
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. 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.
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Public notes
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Contacts
Principal investigator
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Address
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Hoffmann-La Roche
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Country
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Fax
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Email
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01107418
Download to PDF