Phase 2
N=130
An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer
Lung Cancer, Non-Small Cell
Bottom Line
View on ClinicalTrials.gov: NCT01362296 ↗Enrolled (actual)
130
Serious AEs
34.8%
Results posted
May 2014
Primary outcome: Primary: Progression-Free Survival (PFS) as Assessed by the Investigator (INV) — 11.7; 11.4 Weeks — p=0.5197
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK1120212 (Drug); docetaxel (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Sep 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-Free Survival (PFS) as Assessed by the Investigator (INV) |
11.7; 11.4 | 0.5197 |
| SECONDARY Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase |
57; 21; 4; 1; 0; 0 | — |
| SECONDARY Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase |
15; 1; 4; 0; 0; 0 | — |
| SECONDARY Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY 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 |
1; 0; 40; 23; 46; 20 | — |
| SECONDARY 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 |
0; 0; 15; 1; 8; 0 | — |
| SECONDARY 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 |
0; 0; 0; 0; 0; 3 | — |
| SECONDARY 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 |
0; 0; 1; 0; 2; 1 | — |
| SECONDARY Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase |
87; 43; 32; 9 | — |
| SECONDARY Number of Participants With Any SAE or Non-serious AE: Crossover Phase |
22; 2; 12; 1 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase |
13.5; 3.1; 10.7; 2.5 | — |
| SECONDARY Change From Baseline in SBP and DBP: Crossover Phase |
8.7; -15.0; 8.3; -12.0 | — |
| SECONDARY Change From Baseline in Heart Rate: Randomized Phase |
10.4; 13.2 | — |
| SECONDARY Change From Baseline in Heart Rate: Crossover Phase |
8.5; 5.0 | — |
| SECONDARY Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase |
0; 0; 10; 5 | — |
| SECONDARY Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase |
0; 0; 1; 0 | — |
| SECONDARY Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase |
6.7; 12.4 | — |
| SECONDARY Overall Survival (OS) |
8.1; 9.9 | — |
| SECONDARY GSK1120212 Plasma Pharmacokinetic (PK) Concentration |
16.1; 21.5; 29.7; 24.8; 16.7; 12.9 | — |
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.
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) v1.1.
- 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.
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).
Data sourced from ClinicalTrials.gov (NCT01362296). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.