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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Carboplatin; Drug: Docetaxel; Drug: Cisplatin; Drug: nab-Paclitaxel; Drug: Trametinib (GSK1120212); Drug: Erlotinib

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2010
• Primary Completion (Actual): October 7, 2013
• Study Completion (Actual): October 7, 2013

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: August 30, 2010
• First Posted (Estimate): August 31, 2010

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Docetaxel; Cisplatin; Erlotinib; Carboplatin; Trametinib; Pemetrexed; MEK inhibitor; Abraxane; KRAS; Tarceva; nab-Paclitaxel; Taxotere; GSK1120212; Alimta
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Folic Acid Antagonists; Docetaxel; Carboplatin; Paclitaxel; Erlotinib Hydrochloride; Pemetrexed; Trametinib
• Other Study ID Numbers: 113486; 2012-000257-32 (EudraCT Number)