Clinical trial NCT00949702: A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-07-30
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
timeFrame: From first treatment through September 27, 2010
Secondary outcomes:
measure: Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
timeFrame: From first treatment through September 27, 2010
measure: Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
timeFrame: From first treatment through September 27, 2010
measure: Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
timeFrame: From first treatment through September 27, 2010
measure: Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
timeFrame: From first treatment through September 27, 2010
measure: Overall Survival
timeFrame: From first treatment through September 27, 2010
measure: 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
timeFrame: From first treatment through September 27, 2010
measure: Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1
timeFrame: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
measure: Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1
timeFrame: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
measure: Vemurafenib Plasma Levels at Various Treatment Cycles
timeFrame: Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
measure: Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)
timeFrame: Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
measure: Percentage of Patients With Adverse Event
timeFrame: From first treatment through September 27, 2010
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA - School of Medicine; Division of Hematology/Oncology
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital;Hematology/ Oncology
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Inst. ; Dept. of Medical Oncology
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the Uni of Pennsylvania; Section of Hematology/Oncology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Ctr
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle; Melanoma Clinic
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital; Medical Oncology and Pallative Care
state: New South Wales
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute; Medical Oncology
state: Victoria
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.