Lapatinib Plus Trametinib in KRAS Mutant NSCLC

NCT02230553 | Completed Phase 1

• 1 other identifier: NL49551.031.14
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence rate of dose-limiting toxicities

  1.5 years

• progression free survival

  2.5 years

• overall response rate

  2.5 years

Secondary Outcomes (5)

• 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

Study Arms (1)

lapatinib + trametinib

EXPERIMENTAL

lapatinib: oral tablets, once daily trametinib: oral tablets, once daily

Drug: Lapatinib; Drug: trametinib

Interventions

Lapatinib DRUG

lapatinib + trametinib

trametinib DRUG

lapatinib + trametinib

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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%

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

The Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Lapatinib; trametinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• F Opdam, MD, PhD

  The Netherlands Cancer Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2014
• First Posted: September 3, 2014
• Study Start: October 7, 2014
• Primary Completion: July 29, 2019
• Study Completion: August 6, 2019
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

NL (1)