Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma

NCT01909453

Last updated date
Study Location
University of Alabama Comprehensive Cancer Center SC-2
Birmingham, Alabama, 35294, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Melanoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV)

- Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization

- Naïve untreated patients or patients who have progressed on or after prior first line immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy or chemotherapy), except the administration of BRAF or MEK inhibitors

- Evidence of at least one measurable lesion as detected by radiological or photographic methods

- ECOG performance status of 0 or 1

- Adequate bone marrow, organ function, cardiac and laboratory parameters

- Normal functioning of daily living activities

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Any untreated central nervous system (CNS) lesion


- Uveal and mucosal melanoma


- History of leptomeningeal metastases


- History of or current evidence of central serous retinopathy (CSR), retinal vein
occlusion (RVO) or history of retinal degenerative disease


- Any previous systemic chemotherapy treatment, extensive radiotherapy or
investigational agent other than immunotherapy, or patients who have received more
than one line of immunotherapy for locally advanced unresectable or metastatic
melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at
least 6 weeks prior to randomization


- History of Gilbert's syndrome


- Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor


- Impaired cardiovascular function or clinically significant cardiovascular diseases


- Uncontrolled arterial hypertension despite medical treatment


- HIV positive or active Hepatitis B, and/or active Hepatitis C


- Impairment of gastrointestinal function


- Patients with neuromuscular disorders that are associated with elevated CK


- Pregnant or nursing (lactating) women


- Medical, psychiatric, cognitive or other conditions that may compromise the patient's
ability to understand the patient information, give informed consent, comply with the
study protocol or complete the study


Other protocol-defined inclusion/exclusion criteria may apply

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Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

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MelanomaStudy Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
NCT01909453
  1. Birmingham, Alabama
  2. Phoenix, Arizona
  3. Fayetteville, Arkansas
  4. Los Angeles, California
  5. Orange, California
  6. Greenwood Village, Colorado
  7. Boynton Beach, Florida
  8. Miami, Florida
  9. Chicago, Illinois
  10. Park Ridge, Illinois
  11. Goshen, Indiana
  12. Sioux City, Iowa
  13. Metairie, Louisiana
  14. Boston, Massachusetts
  15. Grand Rapids, Michigan
  16. Rochester, Minnesota
  17. Hattiesburg, Mississippi
  18. Jackson, Mississippi
  19. Lincoln, Nebraska
  20. Omaha, Nebraska
  21. Brick, New Jersey
  22. Hackensack, New Jersey
  23. Bronx, New York
  24. Rochester, New York
  25. Troy, New York
  26. Fargo, North Dakota
  27. Oklahoma City, Oklahoma
  28. Tulsa, Oklahoma
  29. Bethlehem, Pennsylvania
  30. Pittsburgh, Pennsylvania
  31. Sioux Falls, South Dakota
  32. Memphis, Tennessee
  33. Dallas, Texas
  34. Dallas, Texas
  35. Houston, Texas
  36. Colchester, Vermont
  37. Fairfax, Virginia
  38. Wenatchee, Washington
  39. Caba, Buenos Aires
  40. Rosario, Sante Fe
  41. Buenos Aires,
  42. Gateshead, New South Wales
  43. Southport, Queensland
  44. Woolloongabba, Queensland
  45. Woodville, South Australia
  46. Prahran, Victoria
  47. Nedlands, Western Australia
  48. Salvador, BA
  49. Recife, PE
  50. Rio de Janeiro, RJ
  51. Natal, RN
  52. Ijuí, RS
  53. Porto Alegre, RS
  54. Barretos, SP
  55. Sao Paulo, SP
  56. Calgary, Alberta
  57. Toronto, Ontario
  58. Toronto, Ontario
  59. Montreal, Quebec
  60. Montreal, Quebec
  61. Quebec,
  62. Bogotá,
  63. Ostrava Poruba, Czech Republic
  64. Olomouc, CZE
  65. Brno,
  66. Praha 10,
  67. Praha 2,
  68. Paris, Cedex 10
  69. Bordeaux Cedex,
  70. Boulogne Billancourt,
  71. Grenoble Cédex 9,
  72. Le Mans Cedex 09,
  73. LILLE Cedex,
  74. Lyon Cedex,
  75. Nice Cedex 3,
  76. Pierre-Benite Cedex,
  77. Reims,
  78. Strasbourg,
  79. Villejuif Cedex,
  80. Mannheim, Baden-Württemberg
  81. Magdeburg, Sachen-Anhalt
  82. Bayreuth,
  83. Berlin,
  84. Bonn,
  85. Dresden,
  86. Erfurt,
  87. Essen,
  88. Frankfurt,
  89. Freiburg,
  90. Gera,
  91. Hamburg,
  92. Hannover,
  93. Heidelberg,
  94. Homburg,
  95. Kassel,
  96. Kiel,
  97. Leipzig,
  98. Lübeck,
  99. Mainz,
  100. Minden,
  101. Muenchen,
  102. Muenster,
  103. Nuernberg,
  104. Regensburg,
  105. Stade,
  106. Tübingen,
  107. Ulm,
  108. Würzburg,
  109. Athens, GR
  110. Athens, GR
  111. Budapest,
  112. Budapest,
  113. Debrecen,
  114. Szolnok,
  115. Haifa,
  116. Jerusalem,
  117. Ramat Gan,
  118. Ancona, AN
  119. Bari, BA
  120. Bergamo, BG
  121. Brescia, BS
  122. Genova, GE
  123. Lecco, LC
  124. Monza, MB
  125. Milano, MI
  126. Milano, MI
  127. Milano, MI
  128. Palermo, PA
  129. Padova, PD
  130. Pisa, PI
  131. Parma, PR
  132. Pavia, PV
  133. Ragusa, RG
  134. Roma, RM
  135. Roma, RM
  136. Roma, RM
  137. Siena, SI
  138. Candiolo, TO
  139. Terni, TR
  140. Udine, UD
  141. Bologna,
  142. Napoli,
  143. Fukuoka-city, Fukuoka
  144. Matsumoto, Nagano
  145. Chuo-ku, Tokyo
  146. Niigata,
  147. Osaka,
  148. Seoul, Korea
  149. Seoul, Korea
  150. Seoul, Korea
  151. Seoul, Korea
  152. México, Distrito Federal
  153. México, Distrito Federal
  154. Monterrey, Nuevo León
  155. Cancun, Quintana Roo
  156. Amsterdam,
  157. Breda,
  158. Eindhoven,
  159. Enschede,
  160. Groningen,
  161. Heerlen,
  162. Leeuwarden,
  163. Leiden,
  164. Maastricht,
  165. Nijmegen,
  166. Rotterdam,
  167. Utrecht,
  168. Zwolle,
  169. Oslo,
  170. Warszawa,
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  172. Lisboa,
  173. Lisboa,
  174. Porto,
  175. Moscow,
  176. Ryazan,
  177. St. Petersburg,
  178. Singapore,
  179. Bratislava, Slovak Republic
  180. Poprad,
  181. Pretoria,
  182. Pretoria,
  183. Granada, Andalucia
  184. Jerez de La Frontera, Andalucia
  185. Sevilla, Andalucia
  186. Sevilla, Andalucia
  187. Oviedo, Asturias
  188. Lleida, Cataluna
  189. Badalona, Catalunya
  190. Barcelona, Catalunya
  191. Barcelona, Catalunya
  192. Alicante, Comunidad Valenciana
  193. Valencia, Comunidad Valenciana
  194. Valencia, Comunidad Valenciana
  195. La Coruna, Galicia
  196. Lugo, Galicia
  197. Majadahonda, Madrid
  198. El Palmar, Murcia
  199. Pamplona, Navarra
  200. San Sebastián, Pais Vasco
  201. Barcelona,
  202. Madrid,
  203. Madrid,
  204. Madrid,
  205. Madrid,
  206. Santa Cruz de Tenerife,
  207. Gavle,
  208. Goteborg,
  209. Linköping,
  210. Lund,
  211. Stockholm,
  212. Uppsala,
  213. Aarau, Aargau
  214. Bern,
  215. Zürich,
  216. Ankara,
  217. Antalya,
  218. Izmir,
  219. Broomfield, Chelmsford
  220. Surrey, England
  221. Northwood, Middlesex
  222. Cambridge,
  223. Leeds,
  224. London,
  225. London,
  226. Manchester,
  227. Merseyside,
  228. Oxford,
  229. Preston,
  230. Sheffield,
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Advanced Information
Descriptive Information
Brief Title  ICMJE Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
Official Title  ICMJE A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Brief Summary

This is 2-part, randomized, open label, multi-center, parallel group, phase III study comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818 monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. A total of approximately 900 patients will be randomized.

Part 1:

Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms:

  1. LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm)
  2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or
  3. vemurafenib 960 mg BID (denoted as vemurafenib arm)

Part 2:

Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms:

  1. LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or
  2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: LGX818
    LGX818- Orally 100 mg and 50 mg capsules
  • Drug: MEK162
    MEK162- Orally 15 mg tablets
  • Drug: vemurafenib
    Tablets in bottles or blisters 240 mg
    Other Names:
    • Zelboraf
    • PLX4032
    • RO5185426
Study Arms  ICMJE
  • Experimental: LGX818 450 mg + MEK162
    LGX818 450 mg QD + MEK162 45 mg BID
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
  • Active Comparator: Vemurafenib
    Vemurafenib 960 mg BID
    Intervention: Drug: vemurafenib
  • Experimental: LGX818 300 mg + MEK162
    LGX818 300 mg QD + MEK162 45 mg BID
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
  • Experimental: LGX818
    LGX818 300 mg QD
    Intervention: Drug: LGX818
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 3, 2016)
921
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2013)
900
Estimated Study Completion Date  ICMJE January 2024
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV)
  • Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization
  • Naïve untreated patients or patients who have progressed on or after prior first line immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy or chemotherapy), except the administration of BRAF or MEK inhibitors
  • Evidence of at least one measurable lesion as detected by radiological or photographic methods
  • ECOG performance status of 0 or 1
  • Adequate bone marrow, organ function, cardiac and laboratory parameters
  • Normal functioning of daily living activities

Exclusion Criteria:

  • Any untreated central nervous system (CNS) lesion
  • Uveal and mucosal melanoma
  • History of leptomeningeal metastases
  • History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease
  • Any previous systemic chemotherapy treatment, extensive radiotherapy or investigational agent other than immunotherapy, or patients who have received more than one line of immunotherapy for locally advanced unresectable or metastatic melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at least 6 weeks prior to randomization
  • History of Gilbert's syndrome
  • Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor
  • Impaired cardiovascular function or clinically significant cardiovascular diseases
  • Uncontrolled arterial hypertension despite medical treatment
  • HIV positive or active Hepatitis B, and/or active Hepatitis C
  • Impairment of gastrointestinal function
  • Patients with neuromuscular disorders that are associated with elevated CK
  • Pregnant or nursing (lactating) women
  • Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   Colombia,   Czechia,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01909453
Other Study ID Numbers  ICMJE CMEK162B2301
C4221004 ( Other Identifier: Pfizer )
2013-001176-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP