Lapatinib Plus Trametinib in KRAS Mutant NSCLC (M14LTK)

Phase I/II Study With Lapatinib Plus Trametinib in Patients With Metastatic KRAS Mutant Non-small Cell Lung Cancer

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Lapatinib; Drug: trametinib

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: F Opdam, MD,PhD; Phone Number: 0031205122446; Email: f.opdam@nki.nl
• Study Contact Backup: Name: S huijberts, MD; Phone Number: 0031205129111; Email: s.huijberts@nki.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Recruiting
    • The Netherlands Cancer Institute
    • Contact: N HM Steeghs, MD, PhD; Phone Number: 0031205122446; Email: n.steeghs@nki.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lapatinib + trametinib; lapatinib: oral tablets, once daily trametinib: oral tablets, once daily	Drug: Lapatinib; Drug: trametinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall response rate	2.5 years
Incidence rate of dose-limiting toxicities	1.5 years
progression free survival	2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
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

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: f opdam, MD, PhD, The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: August 29, 2014
• First Posted (Estimate): September 3, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib; Lapatinib
• Other Study ID Numbers: NL49551.031.14