An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer

NCT01362296 | Completed Phase 2 Results

• 1 other identifier: 114653
• Study Type: interventional
• Target: 134
• Locations: 8 countries
• Sites: 60

Brief Summary

This is a phase II, open-label, multicenter, randomized study to evaluate the efficacy and safety of GSK1120212 compared with docetaxel in the second line setting for subjects with locally advanced or metastatic (Stage IV) Non-small cell lung cancer (NSCLC) harboring a KRAS mutation who have failed one platinum-containing chemotherapy regimen. A small subset of NSCLC subjects harboring BRAF, NRAS, or MEK1 mutations will be randomized in addition to the primary KRAS population, for exploratory purposes.

Conditions

Lung Cancer, Non-Small Cell

Keywords

NRAS; docetaxel; NSCLC; GSK1120212; MEK inhibitor; targeted therapy; KRAS; BRAF

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) as Assessed by the Investigator (INV)

  PFS is defined as the time from RAN until the earliest date of documented radiological PD or DT due to any cause. PD was assessed by the INV according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. For participants (PAR) who did not have a documented date of PD or DT, PFS was censored at the date of the last adequate assessment. For PAR who received subsequent anti-cancer therapy prior to the date of documented PD or DT, PFS was censored at the date of the last adequate assessment prior to the initiation of therapy.

  From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)

Secondary Outcomes (19)

• Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase

  Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

• Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase

  Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

• Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase

  Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

• Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase

  Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

• Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase

  Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Study Arms (2)

GSK1120212

EXPERIMENTAL

Oral once daily

Drug: GSK1120212

docetaxel

ACTIVE COMPARATOR

IV once every 3 weeks

Drug: docetaxel

Interventions

GSK1120212 DRUG

Oral once daily

GSK1120212

docetaxel DRUG

IV once every 3 weeks

docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years old with histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage IV NSCLC with a positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene.
• Documented tumor progression after receiving at least one, but not more than one, prior approved platinum-containing chemotherapy regimen for advanced stage/metastatic NSCLC.
• Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Life expectancy of at least three months in the opinion of the investigator.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization to study treatment and agree to use effective contraception. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the time of randomization to study medication until at least four weeks after the last dose of study treatment.
• Adequate baseline organ function.

You may not qualify if:

• History of another malignancy.
• Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• Treatment with a BRAF or MEK inhibitor or docetaxel as monotherapy or as part of a combination regimen.
• Anti-cancer therapy (including chemotherapy and radiation therapy) within the last three weeks.
• History or current evidence / risk of retinal vein occlusion or central serous retinopathy.
• Any current or history of tumor manifestation in the Central Nervous System.
• History or evidence of cardiovascular risk, including QTcB \>=480 msec, uncontrolled arrhythmias, acute coronary syndrome, coronary angioplasty, or stenting within 6 months prior to randomization, \>=Class II congestive heart failure, treatment refractory hypertension, intra-cardiac defibrillators or permanent pacemakers or cardiac metastases.
• Known Human Immunodeficiency Virus, Hepatitis B Virus (HBV), or Hepatitis C Virus (HBC) infection (with the exception of chronic or cleared HBV and HCV infection).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (60)

GSK Investigational Site

Scottsdale, Arizona, 85259, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32224, United States

Location

GSK Investigational Site

Athens, Georgia, 30607, United States

Location

GSK Investigational Site

Coeur d'Alene, Idaho, 83814, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21231-2410, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Portland, Oregon, 97239, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19141, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38120, United States

Location

GSK Investigational Site

Austin, Texas, 78731, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Fairfax, Virginia, 22031, United States

Location

GSK Investigational Site

Vancouver, Washington, 98684, United States

Location

GSK Investigational Site

Marseille, 13915, France

Location

GSK Investigational Site

Paris, 75230, France

Location

GSK Investigational Site

Paris, 75908, France

Location

GSK Investigational Site

Paris, 75970, France

Location

GSK Investigational Site

Strasbourg, 67091, France

Location

GSK Investigational Site

Toulouse, 31059, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Athens, 115 22, Greece

Location

GSK Investigational Site

Athens, 115 27, Greece

Location

GSK Investigational Site

Heraklion, Crete, 71110, Greece

Location

GSK Investigational Site

Neo Faliro, 18547, Greece

Location

GSK Investigational Site

Thessaloniki, 57010, Greece

Location

GSK Investigational Site

Budapest, 1529, Hungary

Location

GSK Investigational Site

Székesfehérvár, 8000, Hungary

Location

GSK Investigational Site

Törökbálint, 2045, Hungary

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20133, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Amsterdam, 1081 HV, Netherlands

Location

GSK Investigational Site

Breda, 4818 CK, Netherlands

Location

GSK Investigational Site

Groningen, 9713 GZ, Netherlands

Location

GSK Investigational Site

Maastricht, 6229 HX, Netherlands

Location

GSK Investigational Site

Zwolle, 8011 JW, Netherlands

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Seoul, 138-736, South Korea

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

Location

GSK Investigational Site

Pamplona, 31008, Spain

Location

Related Publications (1)

• Blumenschein GR Jr, Smit EF, Planchard D, Kim DW, Cadranel J, De Pas T, Dunphy F, Udud K, Ahn MJ, Hanna NH, Kim JH, Mazieres J, Kim SW, Baas P, Rappold E, Redhu S, Puski A, Wu FS, Janne PA. A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)dagger. Ann Oncol. 2015 May;26(5):894-901. doi: 10.1093/annonc/mdv072. Epub 2015 Feb 26.

  PMID: 25722381 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

trametinib; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: May 30, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2013
• Last Updated: July 11, 2014
• Results First Posted: May 26, 2014

Record last verified: 2014-06

Locations

US (25); IT (3); FR (7); NL (6); KR (4); GR (5); ES (7); HU (3)