Safety and Tolerability Study of GSK1120212, a MEK Inhibitor, in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel

Study Description

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Brief Summary:

The purpose of this study is to determine what dose of GSK1120212 can be given safely in combination with at least one other drug that is already approved to treat cancer. This study will test the safety of up to 6 different GSK1120212 study treatment combinations (GSK1120212 plus either docetaxel, erlotinib, pemetrexed, pemetrexed + carboplatin, pemetrexed + cisplatin, or nab-paclitaxel). The doses identified in this study may be used in future trials to test whether the combination treatment is a safe and effective therapy for subjects with metastatic lung and/or pancreatic cancers.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: Trametinib (GSK1120212); Drug: Docetaxel; Drug: Erlotinib; Drug: Pemetrexed; Drug: Carboplatin; Drug: nab-Paclitaxel; Drug: Cisplatin	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	169 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-Label, Phase I/Ib Dose Escalation Study to Assess the Safety and Tolerability of GSK1120212 in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel in Subjects With Advanced Solid Tumors
Actual Study Start Date :	September 14, 2010
Actual Primary Completion Date :	October 7, 2013
Actual Study Completion Date :	October 7, 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Treatment Group 1; Trametinib plus Docetaxel	Drug: Trametinib (GSK1120212); Investigational small molecule targeted therapy (MEK1/2 inhibitor) Drug: Docetaxel; Chemotherapy
Experimental: Treatment Group 2; Trametinib plus Erlotinib	Drug: Trametinib (GSK1120212); Investigational small molecule targeted therapy (MEK1/2 inhibitor) Drug: Erlotinib; Small molecule targeted therapy (EGFR inhibitor)
Experimental: Treatment Group 3; Trametinib plus Pemetrexed	Drug: Trametinib (GSK1120212); Investigational small molecule targeted therapy (MEK1/2 inhibitor) Drug: Pemetrexed; Chemotherapy
Experimental: Treatment Group 4; Trametinib plus Pemetrexed and Carboplatin	Drug: Trametinib (GSK1120212); Investigational small molecule targeted therapy (MEK1/2 inhibitor) Drug: Pemetrexed; Chemotherapy Drug: Carboplatin; Chemotherapy
Experimental: Treatment Group 5; Trametinib plus nab-Paclitaxel	Drug: Trametinib (GSK1120212); Investigational small molecule targeted therapy (MEK1/2 inhibitor) Drug: nab-Paclitaxel; Chemotherapy
Experimental: Treatment Group 6; Trametinib plus Pemetrexed and Cisplatin	Drug: Trametinib (GSK1120212); Investigational small molecule targeted therapy (MEK1/2 inhibitor) Drug: Pemetrexed; Chemotherapy Drug: Cisplatin; Chemotherapy

Outcome Measures

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Primary Outcome Measures :

1. To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination [ Time Frame: Duration of study (approximately 3 years) ]

Secondary Outcome Measures :

1. To characterize population pharmacokinetic parameters [ Time Frame: Duration of study (approximately 3 years) ]
2. To evaluate the anti-tumor activity as assessed by tumor response rate according to RECIST v1.1 [ Time Frame: Duration of study (approximately 3 years) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• The subject has a solid tumor. Expansion cohorts are limited to non-small cell lung cancer and/or pancreatic cancer with or without a KRAS mutation.
• Tumor progression following at least one prior standard therapy, the subject refuses standard therapy, or no standard therapy exists.
• The subject has a radiographically measurable tumor.
• The subject is able to carry out daily life activities without difficulty.
• The subject is able to swallow and retain oral medication.
• The subject does not have significant side effects from previous anti-cancer treatment.
• The subject has adequate organ and blood cell counts.
• Sexually active subjects must use medically acceptable methods of contraception during the course of the study.

Exclusion Criteria:

• The subject has had major surgery or received certain types of cancer therapy within 2-3 weeks before starting the study.
• The subject has a brain tumor.
• Current severe, uncontrolled systemic disease.
• History of clinically significant heart, lung, or eye/vision problems.
• The subject has high blood pressure that is not well-controlled with medication.
• The subject has a permanent pacemaker.
• The subject is pregnant or breastfeeding.
• Positive for Hepatitis B, Hepatitis C, or HIV.

Contacts and Locations

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Locations

United States, Arizona
GSK Investigational Site
Scottsdale, Arizona, United States, 85259
United States, California
GSK Investigational Site
Duarte, California, United States, 91010
GSK Investigational Site
Sacramento, California, United States, 95817
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80218
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89169
United States, New York
GSK Investigational Site
Albany, New York, United States, 12206
United States, South Carolina
GSK Investigational Site
Greenville, South Carolina, United States, 29605
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75246
GSK Investigational Site
Houston, Texas, United States, 77030
GSK Investigational Site
Tyler, Texas, United States, 75702
United States, Virginia
GSK Investigational Site
Norfolk, Virginia, United States, 23502
United States, Washington
GSK Investigational Site
Vancouver, Washington, United States, 98684
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
France
GSK Investigational Site
Caen Cedex 9, France, 14033
GSK Investigational Site
Marseille cedex 5, France, 13385
GSK Investigational Site
Saint-Herblain cedex, France, 44805
GSK Investigational Site
Toulouse cedex, France, 31052
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
GSK Investigational Site
Seoul, Korea, Republic of, 135-710

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Additional Information:

Results for study 113486 can be found on the GSK Clinical Study Register. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gandara DR, Leighl N, Delord JP, Barlesi F, Bennouna J, Zalcman G, Infante JR, Reckamp KL, Kelly K, Shepherd FA, Mazieres J, Janku F, Gardner OS, Mookerjee B, Wu Y, Cox DS, Schramek D, Peddareddigari V, Liu Y, D'Amelio AM Jr, Blumenschein G Jr. A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2017 Mar;12(3):556-566. doi: 10.1016/j.jtho.2016.11.2218. Epub 2016 Nov 19.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01192165 History of Changes
Other Study ID Numbers:	113486; 2012-000257-32 ( EudraCT Number )
First Posted:	August 31, 2010
Last Update Posted:	November 13, 2017
Last Verified:	November 2017

Keywords provided by GlaxoSmithKline:

Taxotere; Cisplatin; Carboplatin; Trametinib; GSK1120212; Tarceva; KRAS	Pemetrexed; MEK inhibitor; nab-Paclitaxel; Docetaxel; Alimta; Abraxane; Erlotinib

Additional relevant MeSH terms:

Paclitaxel; Docetaxel; Trametinib; Albumin-Bound Paclitaxel; Cisplatin; Carboplatin; Erlotinib Hydrochloride; Pemetrexed; Antineoplastic Agents, Phytogenic	Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors