Phase I/II Study With Lapatinib Plus Trametinib in Patients With Metastatic KRAS Mutant Non-small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Lapatinib
- Conditions
- Colorectal Cancer
- Sponsor
- The Netherlands Cancer Institute
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- overall response rate
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
This is an open-label phase I/II multi-center study consisting of two parts. Part A of this study is designed to identify the recommended phase 2 dose (RP2D) of lapatinib combined with trametinib in patients with metastatic KRASm and PIK3CA wild-type (PIK3CAwt) non-small cell lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the lapatinib-trametinib combination versus standard of care therapy in patients with metastatic KRASm/PIK3CAwt NSCLC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histological or cytological proof of metastatic NSCLC; for PART B: treated with first line therapy for metastatic disease only.
- •Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wild-type (exon 9 and 20)
- •Age ≥ 18 years
- •Able and willing to give written informed consent
- •WHO performance status of 0 or 1 (part A and B)
Exclusion Criteria
- •Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment.
- •History of another primary malignancy
- •Symptomatic or untreated leptomeningeal disease
- •Symptomatic brain metastasis
- •History of interstitial lung disease or pneumonitis
- •Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients
- •Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), or a history of uveitis, retinal vein occlusion, central serous retinopathy, or retinal detachment
- •Patients with left ventricular ejection fraction (LVEF) \< 50%
Arms & Interventions
lapatinib + trametinib
lapatinib: oral tablets, once daily trametinib: oral tablets, once daily
Intervention: Lapatinib
lapatinib + trametinib
lapatinib: oral tablets, once daily trametinib: oral tablets, once daily
Intervention: trametinib
Outcomes
Primary Outcomes
overall response rate
Time Frame: 2.5 years
progression free survival
Time Frame: 2.5 years
Incidence rate of dose-limiting toxicities
Time Frame: 1.5 years
Secondary Outcomes
- Incidence and severity of adveres events(2.5 years)
- Plasma concentration(2.5 years)
- Duration of response(2.5 years)
- Time to response(2.5 years)
- Overall survival(3 years)