Paclitaxel-trastuzumab in EGFR-mutated NSCLC Patients

Paclitaxel-trastuzumab in EGFR-mutated NSCLC Patients After Progression on TKI-treatment; a Pilot-study

This study is a pilot study in EGFR-mutated NSCLC patients who have progressed on standard-dose TKIs. Tumor biopsies will be evaluated for HER2-expression. In case of HER2 expression, patients can participate in the trial after obtaining informed consent.

Patients will be treated with weekly paclitaxel-trastuzumab.

Study Overview

• Status: Unknown
• Conditions: NSCLC; EGFR-mutation; HER2-expression
• Intervention / Treatment: Drug: Paclitaxel-trastzumab

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1007MB
    • VU University Medical Center

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:

• Histologically confirmed stage IV non-squamous NSCLC patients.
• Patients must have been detected with an activating EGFR mutation at baseline and must have yet progressed on erlotinib, gefitinib or afatinib monotherapy in daily dose of 150 mg, 250 mg or 40 mg respectively. (Patients with unknown mutation status that have exhibited a response to these agents or stable disease for at least 6 months while on treatment with gefitinib or erlotinib are also eligible).
• Rebiopsy after having acquired resistance to TKI-treatment must have been performed and HER2-overexpression (positive immunohistochemistry staining) must have been detected.
• There must be at least one measurable disease site, according to RECIST 1.1 criteria.
• WHO performance status 0-2.
• Willing and able to comply with the study prescriptions.
• 18 years or older.
• Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study.
• Ability to give written informed consent before patient registration.

Exclusion Criteria:

• No uncontrolled infectious disease.
• No other active malignancy.
• No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy or VATS biopsy) in the previous 4 weeks.
• No treatment with investigational drugs.
• No known hypersensitivity to trastuzumab-paclitaxel
• No symptomatic brain metastases.
• History of coronary artery disease, NYHA class III or IV and Left Ventricular Ejection Fraction (LVEF) of <45%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Paclitaxel-trastuzumab; Paclitaxel-trastuzumab weekly	Drug: Paclitaxel-trastzumab; Trastuzumab; Dose:First dose: 4 mg/kg IVSubsequent doses: 2 mg/kg every week IV.; The patient must be monitored for at least 6 hours after the start of the first infusion and for at least 2 hours after the start of subsequent infusions. Paclitaxel - Dose: 60 mg/m2 IV in 30 minutes, every week, after trastuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity	2 years
progression-free survival	2 years
Disease control rate	6 weeks

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ANTICIPATED): August 1, 2016

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: August 25, 2014
• First Posted (ESTIMATE): August 27, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): August 27, 2014
• Last Update Submitted That Met QC Criteria: August 25, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: NSCLC; Trastuzumab; Paclitaxel; HER2-expression; EGFR-mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: HER2-targeting in EGFR-mutated