Last updated: 11/03/2018 16:24:46
GSK1120212 vs chemotherapy in advanced or metastatic BRAF V600E/K mutation-positive melanoma
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase III randomized, open-label study comparing GSK1120212 to chemotherapy in subjects with advanced or metastatic BRAF V600E/K mutation-positive melanoma
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Progression-free survival in BRAF V600E mutation-positive participants without a history of brain metastases as assessed by the Investigator and Independent Review
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Secondary outcomes:
Progression-free survival in all participants
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
PFS in BRAF V600E mutation-positive participants without a history of brain metastases and without prior chemotherapy as assessed by the Investigator
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
PFS in BRAF V600E mutation-positive participants without a history of brain metastases and with prior chemotherapy as assessed by the Investigator
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Overall Survival in all participants
Timeframe: Day 1 until death due to any cause (average of 20.3 months)
Overall Survival in BRAF V600E mutation-positive participants without a history of brain metastases
Timeframe: Day 1 until death due to any cause (average of 20.3 months)
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
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Number of participants with OR as assessed by the Investigator and Independent Review
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Number of BRAF V600E mutation-positive participants classified as confirmed responders (CR and PR) as assessed by the Investigator
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Number of BRAF V600K mutation-positive participants classified as confirmed responders (CR and PR) as assessed by the Investigator
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Number of participants with OR following Cross-over to Trametinib
Timeframe: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
DoR for all confirmed responders (CR or PR) as assessed by the Investigator Review
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
DoR for all confirmed responders (CR or PR) as assessed by the Independent Review
Timeframe: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
DoR for all responders (CR or PR) following cross-over to Trametinib as assessed by the Investigator
Timeframe: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
PFS following cross-over to Trametinib as assessed by the Investigator
Timeframe: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
Interventions:
Enrollment:
322
Primary completion date:
2011-26-10
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Flaherty, K.T., et al. Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma. N Eng J Med. 2012 Jun 4; 10(1056): 1-8
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.
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.
Schadendorf D, Amonkar MM, Milhem M, Grotzinger K, Demidov LV, Rutkowski P, Garbe C, Dummer R, Hassel JC, Wolter P, Mohr P, Trefzer U, Lefeuvre-Plesse C, Rutten A, Steven N, Ullenhag G, Sherman L, Wu FS, Patel K, Casey M, Robert C. Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: Quality of life analyses of the METRIC study. Ann Oncol. 2014;25(3):700-706.
Medical condition
Melanoma
Product
trametinib
Collaborators
Not applicable
Study date(s)
November 2010 to July 2016
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- ≥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
- 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)
Inclusion and exclusion criteria
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
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
- 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
- Evidence of new optic disc cupping.
- Intraocular pressure > 21 mm Hg as measured by tonography
History or evidence of cardiovascular risk including any of the following:
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:
Trial location(s)
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23538
Status
Study Complete
Location
GSK Investigational Site
Garran, Australian Capital Territory, Australia, 2606
Status
Study Complete
Location
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
Status
Study Complete
Location
GSK Investigational Site
Woolloongabba, Queensland, Australia, 4102
Status
Study Complete
Location
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Status
Study Complete
Location
GSK Investigational Site
Kurralta Park, South Australia, Australia, 5037
Status
Study Complete
Location
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Status
Study Complete
Location
GSK Investigational Site
Tucson, Arizona, United States, 85724-5024
Status
Study Complete
Location
GSK Investigational Site
Morristown, New Jersey, United States, 07962-1956
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newtown, Wellington, New Zealand, 6002
Status
Study Complete
Location
GSK Investigational Site
Columbia, South Carolina, United States, 29210
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chattanooga, Tennessee, United States, 37404
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Calgary, Alberta, Canada, T2N 4N2
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Townsville, Queensland, Australia, 4810
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
South Brisbane, Queensland, Australia, 4101
Status
Study Complete
Location
GSK Investigational Site
Marietta, Georgia, United States, 30060
Status
Study Complete
Location
GSK Investigational Site
London, Ontario, Canada, N6A 4L6
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Status
Study Complete
Location
GSK Investigational Site
Waratah, New South Wales, Australia, 2300
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 4E6
Status
Study Complete
Location
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
Status
Study Complete
Location
GSK Investigational Site
Athens, Georgia, United States, 30607
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina, C1121ABE
Status
Recruiting
Location
GSK Investigational Site
Metairie, Louisiana, United States, 70006
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Port Macquarie, New South Wales, Australia, 2444
Status
Study Complete
Location
GSK Investigational Site
Sutton, Surrey, United Kingdom, SM2 5PT
Status
Study Complete
Location
GSK Investigational Site
Fort Myers, Florida, United States, 33916
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
Status
Study Complete
Location
GSK Investigational Site
Northwood, Middlesex, United Kingdom, HA6 2RN
Status
Study Complete
Location
GSK Investigational Site
Memphis, Tennessee, United States, 38120
Status
Study Complete
Location
GSK Investigational Site
Buxtehude, Niedersachsen, Germany, 21614
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2011-26-10
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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Access to clinical trial data by researchers
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