Trastuzumab Therapy in Non-Small Cell Lung Cancer Patients

Prospective Phase II Trial Evaluating Efficacy of Trastuzumab Therapy in HER2 FISH Positive and/or HER2 Mutation Positive, Pretreated, Non-Small Cell Lung Cancer Patients (MO20509)

This is a prospective study assessing efficacy of trastuzumab therapy in pretreated NSCLC patients. Patients with locally advanced or metastatic NSCLC, HER2 FISH positive and/or with HER2 gene mutation, pretreated with at least one previous chemotherapy line will be considered eligible for the trial. After evaluation of inclusion and exclusion criteria, and after signature of informed consensus form, all eligible patients will receive trastuzumab 6 mg/kg every 3 weeks (8 mg/kg loading dose) until disease progression, unacceptable toxicity or patient refusal.

Study Overview

• Status: Terminated
• Conditions: NON-SMALL CELL LUNG CANCER
• Intervention / Treatment: Drug: Trastuzumab (Herceptin)

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas

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 diagnosis of NSCLC. Availability of tumor tissue for HER2 FISH analysis and/or HER2 gene mutation analysis is mandatory

  • Stage IIIB (with effusion) or stage IV or disease relapsed after surgery or radiotherapy and in any case not suitable for radiotherapy or surgery with curative intent
  • HER2 FISH positive defined as high polysomy or gene amplification, or presence of HER2 gene mutation in exon 20
  • At least one measurable lesion
  • Patients pretreated with at least one chemotherapy regimen. Previous therapy with erlotinib or other tyrosine kinase inhibitors is allowed.
  • Patients compliance to trial procedures
  • Age ≥ 18 years
  • Written informed consent
  • Adequate BM function (ANC ≥1.5x109/L, Platelets ≥100x109/L, HgB >9 g/dl)
  • Adequate liver function (bilirubin <G2, transaminases no more than 3xULN/<5xULN in present of liver metastases).
  • Normal level of alkaline phosphatase and creatinine
  • If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [intrauterine contraceptive device (IUD), birth control pills, or barrier device] during and for three months after trial.
  • ECOG performance status 0-1 and life expectancy of at least 3 months
  • Have recovered from the acute, reversible effects of prior surgery or radiotherapy. This means that at least 3 weeks should have elapsed since prior radiotherapy.

Exclusion Criteria:

• • HER2 FISH negative tumor and no evidence of HER2 gene mutation in exon 20

  • Concomitant radiotherapy
  • Untreated brain metastases or leptomeningeal disease involvement.
  • All disease sites previously included in radiotherapy fields. If all sites were included in radiotherapy fields patient is eligible only if there is evidence of progressive disease after completion of radiotherapy.
  • No measurable lesion
  • Left ventricular ejection fraction (FEV) <50%
  • Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin
  • Any previous HER2 blocking therapy. Previous therapy with anti EGFR agents is allowed
  • Pregnancy or lactating
  • Other serious illness or medical condition including: Congestive heart failure (NYHA class II, III, IV) or history of documented congestive heart failure, unstable angina pectoris, myocardial infarction in the last 12 months, poorly controlled hypertension (systolic >180 mmHg or diastolic >100 mmHg), clinically significant valvular heart disease, or high-risk uncontrolled arrhythmias. Patients with dyspnoea at rest due to malignant or other disease (e.g. pulmonary metastases with lymphangitis) or who require supportive oxygen therapy. Active serious uncontrolled infections. Poorly controlled diabetes mellitus
  • Treatment with any investigational drug within 30 days before the beginning of treatment with study drug.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; Trastuzumab 6 mg/Kg	Drug: Trastuzumab (Herceptin); Trastuzumab 6 mg/Kg every 3 weeks i.v. (loading dose 8 mg/Kg i.v.); Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	every two months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to disease progression, overall survival, safety and assessment of biomarkers potentially implicated in trastuzumab sensitivity/resistance	every two months

Collaborators and Investigators

• Sponsor: Armando Santoro, MD

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: September 22, 2008
• First Submitted That Met QC Criteria: September 22, 2008
• First Posted (ESTIMATE): September 23, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): May 29, 2013
• Last Update Submitted That Met QC Criteria: May 27, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: ONC-2007-001; 2007-003709-29