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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01245062




Registration number
NCT01245062
Ethics application status
Date submitted
18/11/2010
Date registered
22/11/2010
Date last updated
5/04/2018

Titles & IDs
Public title
GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma
Scientific title
A Phase III Randomized, Open-label Study Comparing GSK1120212 to Chemotherapy in Subjects With Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma
Secondary ID [1] 0 0
114267
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - GSK1120212
Treatment: Drugs - Chemotherapy

Experimental: GSK1120212 - MEK inhibitor

Active Comparator: Chemotherapy - Investigator Choice of DTIC or paclitaxel

Experimental: Crossover - MEK inhibitor after documented progression on Chemotherapy Arm


Treatment: Drugs: GSK1120212
MEK inhibitor

Treatment: Drugs: Chemotherapy
Investigator Choice of DTIC or paclitaxel
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review
Timepoint [1] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [1] 0 0
Progression-free Survival in All Participants
Timepoint [1] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [2] 0 0
PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator
Timepoint [2] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [3] 0 0
PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator
Timepoint [3] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [4] 0 0
Overall Survival in All Participants
Timepoint [4] 0 0
Day 1 until death due to any cause (average of 20.3 months)
Secondary outcome [5] 0 0
Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases
Timepoint [5] 0 0
Day 1 until death due to any cause (average of 20.3 months)
Secondary outcome [6] 0 0
Number of BRAF V600E Mutation-positive Participants Without a History of Brain Metastases With Overall Response (OR) as Assessed by the Investigator and Independent Review
Timepoint [6] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [7] 0 0
Number of Participants With OR as Assessed by the Investigator and Independent Review
Timepoint [7] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [8] 0 0
Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator
Timepoint [8] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [9] 0 0
Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator
Timepoint [9] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [10] 0 0
Number of Participants With OR Following Cross-over to Trametinib
Timepoint [10] 0 0
Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
Secondary outcome [11] 0 0
Duration of Response (DoR) for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Investigator Review
Timepoint [11] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [12] 0 0
DoR for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Independent Review
Timepoint [12] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [13] 0 0
DoR for All Confirmed Responders (CR or PR) as Assessed by the Investigator Review
Timepoint [13] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [14] 0 0
DoR for All Confirmed Responders (CR or PR) as Assessed by the Independent Review
Timepoint [14] 0 0
Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcome [15] 0 0
DoR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator
Timepoint [15] 0 0
Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
Secondary outcome [16] 0 0
PFS Following Cross-over to Trametinib as Assessed by the Investigator
Timepoint [16] 0 0
Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)

Eligibility
Key inclusion criteria
- =18 years of age

- Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which
is also determined to be BRAF V600E/K mutation-positive by the central laboratory

- Received no prior treatment or up to one prior regimen of chemotherapy for advanced or
metastatic melanoma. Prior treatment with immunotherapy (with the exception of prior
ipilimumab, which is only allowed if given in the adjuvant setting), cytokine therapy,
biological or vaccine regimen is permitted. Prior use of sorafenib is allowed

- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST
1.1)

- Women of childbearing potential and men with reproductive potential must agree to use
effective contraception during the study. Additionally women of childbearing potential
must have a negative serum pregnancy test within 14 days prior to randomization

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

- Adequate screening organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any prior use of BRAF inhibitors or MEK inhibitors.

- Subjects who have received dacarbazine or paclitaxel prior to randomization will not
be eligible to receive the same chemotherapy as study medication (i.e. a subject who
received prior dacarbazine cannot receive dacarbazine on this trial and would thus
receive paclitaxel if randomized to the control arm)

- History of another malignancy. Exception: Subjects who have been disease-free for 3
years, or subjects with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible. Subjects with second malignancies
that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor
if unsure whether second malignancies meet requirements specified above

- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C
Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection
which will be allowed)

- Brain metastases with the following exceptions that are ALL confirmed by the GSK
Medical Monitor:

All known lesions must be previously treated with surgery or stereotactic radiosurgery, and
Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion
size) for =90 days prior to randomization (must be documented with two consecutive MRI or
CT scans using contrast), and asymptomatic with no corticosteroids requirement for = 30
days prior to randomization, and no enzyme-inducing anticonvulsants for = 30 days prior to
randomization

- History or evidence of cardiovascular risk including any of the following:

- QTcB = 480 msec.

- History or evidence of current clinically significant uncontrolled arrhythmias.
Exception: Subjects with controlled atrial fibrillation for >30 days prior to
randomization are eligible

- History of acute coronary syndromes (including myocardial infarction and unstable
angina), coronary angioplasty, or stenting within 6 months prior to
randomization.

- History or evidence of current = Class II congestive heart failure as defined by
New York Heart Association

- History of interstitial lung disease or pneumonitis

- History or current evidence / risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR):

- History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled
glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes
mellitus, or history of hyperviscosity or hypercoagulability syndromes).

- Visible retinal pathology as assessed by ophthalmic exam that is considered a
risk factor for RVO or CSR such as:

- Evidence of new optic disc cupping.

- Intraocular pressure > 21 mm Hg as measured by tonography

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Crossover
Other design features
Phase
Phase 3
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
22/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/12/2016
Sample size
Target
Accrual to date
Final
322
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Garran
Recruitment hospital [2] 0 0
GSK Investigational Site - Port Macquarie
Recruitment hospital [3] 0 0
GSK Investigational Site - Waratah
Recruitment hospital [4] 0 0
GSK Investigational Site - South Brisbane
Recruitment hospital [5] 0 0
GSK Investigational Site - Townsville
Recruitment hospital [6] 0 0
GSK Investigational Site - Woolloongabba
Recruitment hospital [7] 0 0
GSK Investigational Site - Kurralta Park
Recruitment hospital [8] 0 0
GSK Investigational Site - Woodville
Recruitment hospital [9] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [10] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
2300 - Waratah
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
4810 - Townsville
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
5011 - Woodville
Recruitment postcode(s) [9] 0 0
3084 - Heidelberg
Recruitment postcode(s) [10] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
Florida
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United States of America
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Georgia
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United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
Argentina
State/province [11] 0 0
Ciudad Autonoma de Buenos Aires
Country [12] 0 0
Austria
State/province [12] 0 0
Graz
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Austria
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Wien
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussels
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Belgium
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Charleroi
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Belgium
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Gent
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Belgium
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Jette
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Belgium
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Kortrijk
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Leuven
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Wilrijk
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Yvoir
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Canada
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Alberta
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Canada
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British Columbia
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Nova Scotia
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Ontario
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Hradec Kralove
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Ostrava
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Praha 2
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Zlin
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Nantes
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Rennes
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Tours
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France
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Villejuif
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Germany
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Baden-Wuerttemberg
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Bayern
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Niedersachsen
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Sachsen
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Goteborg
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Linkoping
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Lund
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Stockholm
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Uppsala
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Switzerland
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Zurich
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Ukraine
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Dnepropetrovsk
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
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Sumy
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Ukraine
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Sympheropol
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Ukraine
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Ternopil
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Ukraine
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Uzhgorod
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United Kingdom
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Cambridgeshire
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Middlesex
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Surrey
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Aberdeen
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Birmingham
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United Kingdom
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Chelmsford
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Leeds
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London
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United Kingdom
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Manchester
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Oxford
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United Kingdom
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a two-arm, open-label, randomized Phase III study comparing single agent GSK1120212
to chemotherapy (either dacarbazine or paclitaxel) in subjects with Stage IIIc or Stage IV
malignant cutaneous melanoma. All subjects must have a BRAF mutation-positive tumour sample.
Subjects who have received up to one prior regimen of chemotherapy in the advanced or
metastatic melanoma setting will be enrolled into the study. Subjects with any prior BRAF or
MEK inhibitor use will be excluded. Approximately 297 subjects will be enrolled with 2:1
randomization (198 subjects into the GSK1120212 arm and 99 subjects into the chemotherapy
arm). The primary endpoint for the statistical analysis will be a comparison of progression
free survival for subjects receiving GSK1120212 compared to chemotherapy. Subjects who have
progression on chemotherapy will be offered the option to receive GSK1120212.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01245062
Trial related presentations / publications
KT Flaherty, C Robert, P Hersey, P Nathan, C Garbe, M Milhem, L Demidov, J Hassel, P Rutkowski, P Mohr, R Dummer, U Trefzer, JMG Larkin, J Utikal, B Dreno, M Nyakas, MR Middleton, JC Becker, M Casey, LJ Sherman, FS Wu, D Ouellet, AM Martin, K Patel, & D S. MEK inhibition improves survival in Melanoma with activating BRAF Mutations. [N Engl J Med]. 2012;367:107-14.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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/ct2/show/NCT01245062