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

Purpose

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	Intervention	Phase
Cancer	Drug: Trametinib (GSK1120212) Drug: Docetaxel Drug: Erlotinib Drug: Pemetrexed Drug: Carboplatin Drug: nab-Paclitaxel Drug: Cisplatin	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Paclitaxel Carboplatin Docetaxel Pemetrexed Pemetrexed disodium Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination [ Time Frame: Duration of study (approximately 2.5 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To characterize population pharmacokinetic parameters [ Time Frame: Duration of study (approximately 2.5 years) ] [ Designated as safety issue: Yes ]
To evaluate the anti-tumor activity as assessed by tumor response rate according to RECIST v1.1 [ Time Frame: Duration of study (approximately 2.5 years) ] [ Designated as safety issue: No ]

Estimated Enrollment:	166
Study Start Date:	September 2010
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01192165

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

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01192165 History of Changes
Other Study ID Numbers:	113486, 2012-000257-32
Study First Received:	August 30, 2010
Last Updated:	February 14, 2013
Health Authority:	European Union: European Medicines Agency Korea: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) United States: Food and Drug Administration Canada: Health Canada

Keywords provided by GlaxoSmithKline:

Taxotere
Cisplatin
Carboplatin
Trametinib
GSK1120212
Tarceva
KRAS

Pemetrexed
MEK inhibitor
nab-Paclitaxel
Docetaxel
Alimta
Abraxane
Erlotinib

Additional relevant MeSH terms:

Docetaxel
Pemetrexed
Cisplatin
Carboplatin
Paclitaxel
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013