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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00949702




Registration number
NCT00949702
Ethics application status
Date submitted
28/07/2009
Date registered
30/07/2009
Date last updated
25/07/2017

Titles & IDs
Public title
A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
Scientific title
An Open-label Multicenter Study on the Efficacy of Continuous Oral Dosing of Vemurafenib on Tumour Response in Previously Treated Patients With Metastatic Melanoma
Secondary ID [1] 0 0
NP22657
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 - vemurafenib

Experimental: Single arm -


Treatment: Drugs: vemurafenib
960 mg b.i.d. continuous oral dosing
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [1] 0 0
From first treatment through September 27, 2010
Secondary outcome [1] 0 0
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [1] 0 0
From first treatment through September 27, 2010
Secondary outcome [2] 0 0
Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [2] 0 0
From first treatment through September 27, 2010
Secondary outcome [3] 0 0
Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [3] 0 0
From first treatment through September 27, 2010
Secondary outcome [4] 0 0
Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [4] 0 0
From first treatment through September 27, 2010
Secondary outcome [5] 0 0
Overall Survival
Timepoint [5] 0 0
From first treatment through September 27, 2010
Secondary outcome [6] 0 0
Improvement in Physical Symptoms (Improvement in Physician's Assessment of Global Performance Status and Oxygen Saturation Requirements, and Decrease in Total Dose and Frequency of Narcotic Pain Analgesics) During Treatment in Comparison to Baseline
Timepoint [6] 0 0
From first treatment through September 27, 2010
Secondary outcome [7] 0 0
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1
Timepoint [7] 0 0
Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
Secondary outcome [8] 0 0
Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1
Timepoint [8] 0 0
Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
Secondary outcome [9] 0 0
Vemurafenib Plasma Levels at Various Treatment Cycles
Timepoint [9] 0 0
Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
Secondary outcome [10] 0 0
Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)
Timepoint [10] 0 0
Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
Secondary outcome [11] 0 0
Percentage of Patients With Adverse Event
Timepoint [11] 0 0
From first treatment through September 27, 2010

Eligibility
Key inclusion criteria
* adult patients >/=18 years of age
* histologically confirmed metastatic melanoma (Stage IV, AJCC)
* patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
* BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
* measurable disease by RECIST criteria
* negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* active CNS metastases on CT/MRI within 28 days prior to enrollment
* history of or known carcinomatous meningitis
* previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
* cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential
* uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy
* infectious disease including HIV, HBV and HCV

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 2
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
30/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/06/2014
Sample size
Target
Accrual to date
Final
132
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle; Melanoma Clinic - Newcastle
Recruitment hospital [2] 0 0
Westmead Hospital; Medical Oncology and Pallative Care - Westmead
Recruitment hospital [3] 0 0
Peter Maccallum Cancer Institute; Medical Oncology - Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Newcastle
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3000 - 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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas

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 single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma. Patients will receive oral Vemurafenib \[RG7204; PLEXXIKON: PLX4032\] at a dose of 960 mg b.i.d. continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability. Target sample size is \<100 patients.
Trial website
https://clinicaltrials.gov/study/NCT00949702
Trial related presentations / publications
Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.
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.
Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14. doi: 10.1056/NEJMoa1112302.
Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.
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/NCT00949702