Clinical trial NCT01192165: Safety and Tolerability Study of GSK1120212, a MEK Inhibitor, in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Taxotere
Cisplatin
Carboplatin
Trametinib
GSK1120212
Tarceva
KRAS
Pemetrexed
MEK inhibitor
nab-Paclitaxel
Docetaxel
Alimta
Abraxane
Erlotinib
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-08-31
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination
timeFrame: Duration of study (approximately 3 years)
Secondary outcomes:
measure: To characterize population pharmacokinetic parameters
timeFrame: Duration of study (approximately 3 years)
measure: To evaluate the anti-tumor activity as assessed by tumor response rate according to RECIST v1.1
timeFrame: Duration of study (approximately 3 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Tyler
country: United States
facility: GSK Investigational Site
state: Texas
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Vancouver
country: United States
facility: GSK Investigational Site
state: Washington
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Caen Cedex 9
country: France
facility: GSK Investigational Site
city: Marseille cedex 5
country: France
facility: GSK Investigational Site
city: Saint-Herblain cedex
country: France
facility: GSK Investigational Site
city: Toulouse cedex
country: France
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.