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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
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
Secondary ID [1] 0 0
NP25163
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1
Timepoint [1] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Primary outcome [2] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1
Timepoint [2] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1
Primary outcome [3] 0 0
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1
Timepoint [3] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Primary outcome [4] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1
Timepoint [4] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Primary outcome [5] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
Timepoint [5] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Primary outcome [6] 0 0
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9
Timepoint [6] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Primary outcome [7] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9
Timepoint [7] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Primary outcome [8] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15
Timepoint [8] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15
Primary outcome [9] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15
Timepoint [9] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15
Primary outcome [10] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15
Timepoint [10] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Primary outcome [11] 0 0
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15
Timepoint [11] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Primary outcome [12] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15
Timepoint [12] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Primary outcome [13] 0 0
Apparent Clearance (CL/F) of Vemurafenib on Day 15
Timepoint [13] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Primary outcome [14] 0 0
Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15
Timepoint [14] 0 0
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Primary outcome [15] 0 0
Accumulation Ratio of Vemurafenib on Day 15
Timepoint [15] 0 0
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15
Secondary outcome [1] 0 0
Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
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)

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2013
Sample size
Target
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3181 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Rhode Island
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT01107418
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01107418