An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer
Condition: Lung Cancer, Non-Small Cell
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: GSK1120212; docetaxel
Intervention description: Oral once daily; IV once every 3 weeks
Intervention MeSH terms: Docetaxel; Trametinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 134.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NRAS; docetaxel; NSCLC; GSK1120212; MEK inhibitor; targeted therapy; KRAS; BRAF

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).