A Phase II, Open-label, Multicenter, Randomized Study to Assess the Efficacy and Safety of GSK1120212 Compared With Docetaxel in 2nd Line Subjects With Targeted Mutations (KRAS, NRAS, BRAF, MEK1) in Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC Stage IV)

GlaxoSmithKline1 site in 1 country134 target enrollmentSeptember 2011

ConditionsLung Cancer, Non-Small Cell

InterventionsGSK1120212 docetaxel

DrugsGSK1120212 docetaxel

Overview

Phase: Phase 2
Intervention: GSK1120212
Conditions: Lung Cancer, Non-Small Cell
Sponsor: GlaxoSmithKline
Enrollment: 134
Locations: 1
Primary Endpoint: Progression-Free Survival (PFS) as Assessed by the Investigator (INV)
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 2011

End Date

September 2013

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.
•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.

Exclusion Criteria

•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).

Arms & Interventions

GSK1120212

Oral once daily

Intervention: GSK1120212

docetaxel

IV once every 3 weeks

Intervention: docetaxel

Outcomes

Primary Outcomes

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

Time Frame: 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)

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.

Secondary Outcomes

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))
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges 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 With Respect to Normal Ranges 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 With Respect to Normal Ranges 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 Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase(From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months))
Number of Participants With Any SAE or Non-serious AE: Crossover Phase(From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months))
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): 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))
Change From Baseline in SBP and DBP: 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))
Change From Baseline in Heart Rate: 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))
Change From Baseline in Heart Rate: 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 a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase(From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months))
Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase(From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months))
Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase(Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months))
Overall Survival (OS)(Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months))
GSK1120212 Plasma Pharmacokinetic (PK) Concentration(Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose)