First Line Gefitinib by FDG-PET Metabolic Response

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Asan Medical Center
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Sang-We Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01510990
First received: January 10, 2012
Last updated: January 26, 2013
Last verified: January 2013
  Purpose

When considering 1st line gefitinib treatment for NSCLC, the investigators need epidermal growth factor receptor (EGFR) mutational status of the tumor. But most patients do not give us such information at the time of diagnosis, because it requires tumor tissue and some time period for EGFR examination. So, investigators develop a protocol of 1st line gefitinib treatment for NSCLC according to FDG-PET response. If a patient shows 20% or more decrease of peak standard uptake value (SUV) after 1 week's gefitinib treatment, he or she will be continued the treatment. If a patient shows less than 20% decrease of SUV, he or she will be switched to other chemotherapy.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Gefitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: First Line Gefitinib Treatment for Advanced Non-small Cell Lung Cancer (NSCLC) by the FDG-PET Metabolic Response

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Objective Response rate [ Time Frame: one year ] [ Designated as safety issue: No ]
    The primary objective is to see the response rate of gefitinib in the patients who showed % decrease of peak SUV of main lesion 20% or more and continuously treated with gefitinib.


Secondary Outcome Measures:
  • Objective response rate by EGFR mutational status [ Time Frame: One year ] [ Designated as safety issue: No ]
    The secondary object is to see the relationship of changes in FDG uptake after gefitinib treatment with EGFR mutation; sensitivity, specificity, positive predictive value, and negative predictive value will be calculated comparing the groupings created by FDG-PET and actual EGFR mutational status.


Estimated Enrollment: 60
Study Start Date: April 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gefitinib

After a baseline 18F FDG-PET, patients are treated with gefitinib 250mg/d as 1st line treatment for 7 days. And follow up 18F-FDG PET image is acquired after 1 week's treatment of gefitinib (with window period +/- 2 days).

If % decrease of peak SUV of main lesion is 20% or more, gefitinib treatment is continued till progression, unacceptable toxicities or patient's refusal. But if % decrease of peak SUV of main lesion less than 20% or peak SUV increase, gefitinib treatment is stopped, and changed to Pemetrexed/Cisplatin chemotherapy.

Drug: Gefitinib
gefitinib 250mg/day daily
Other Name: Iressa

Detailed Description:

Gefitinib has anti-tumor activity as a result of EGFR tyrosine kinase inhibition, reducing multiple downstream signaling processes that activate cell proliferation and other cell responses, including cell migration angiogenesis, and reduced apoptosis. Recently, it has been approved for the first line treatment of advanced NSCLC that harbors EGFR mutation. In IPASS trial, tumors with EGFR mutation produced 71.2% of clinical response to first line gefitinib while tumors with wild type EGFR showed only 1.1% of response. Therefore, patient selection is critical for the clinical use of EGFR tyrosine kinase inhibitors as first line treatment.

When considering 1st line gefitinib treatment for NSCLC, we need EGFR mutational status of the tumor. But most patients do not give us such information at the time of diagnosis, because it requires tumor tissue and some time period for EGFR examination. So, we need other strategies such as using PET scan for early prediction of response to gefitinib.

Glucose metabolic activity closely reflects responses to gefitinib therapy. In preclinical study with gefitinib sensitive cell lines, there was a dramatic decrease in FDG uptake as early as 2 hours after treatment. And these metabolic alterations preceded changes in cell cycle distribution, thymidine uptake and apoptosis. In contrast, gefitinib resistant cells exhibited no measurable changes in FDG uptake, either in cell culture or in vivo.

The strategy using FDG-PET may guide us to perform 1st line geftinib. Recently investigators reported that FLT-PET or FDG-PET could predict response to EGFR tyrosine kinase (TKI) early after 1 week of treatment. And % decrease more than 20% of maximum SUV of main lesion after 1 week of EGFR TKI treatment could predict response to that drug. More than 20% decrease of SUV is a significant change during reproducibility test and also considered as a criteria for response prediction of paclitaxel/cisplatin chemotherapy.

So, investigators develop a protocol of 1st line gefitinib treatment for NSCLC according to FDG-PET response. And if the patient showed less than 20% decrease of peak SUV, investigators will stop gefitinib and treat him or her with the regimen of pemetrexed/cisplatin.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • More than 18 years of age
  • Advanced or metastatic adenocarcinoma of the lung. Non-smoking or light smoking patients (less than 10 PY smoking and more than 10 years of ex-smoking period) are preferred to enrich the patients with clinical response to gefitinib.
  • Chemonaive patients.
  • At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or and which is suitable for accurate repeated measurements.
  • ECOG PS 0-2
  • Patients with tissue for the detection of EGFR mutation
  • At least 1 week since the last radiotherapy. Patients must have recovered from all acute toxicities from radiotherapy.
  • Patients must have adequate hematologic, renal and liver function as defined by Hb > 9g/dL, neutrophils > 1000/mm3, platelets > 50,000/mm3, creatinine < 2mg/dL, and AST (SGOT) and/or ALT (SGPT) < 5 x UNL (upper normal limit).
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
  • Written and voluntary informed consent understood, signed and dated.

Exclusion criteria

  • Symptomatic brain metastasis. Brain metastases stable < 2 weeks before dosing or requiring concurrent steroid treatment or with clinical symptoms.
  • Major surgery within 3 weeks prior to study enrollment.
  • Previous (less than 3 years ago) or current malignancies at sites other than curatively treated in situ carcinoma of cervix, or basal or squamous cell carcinoma of the skin.
  • Past medical history of interstitial lung diseas, drug induced interstitial disease, radiation pneumonitis which required steroid treatment or any active interstitial lung disease.
  • Pre-existing idiopathic pulmonary fibrosis on CT scans on baseline.
  • Insufficient lung function as determined by either clinical examination or an arterial oxygen tension (PaO2) < 70mmHg.
  • Uncontrolled diabetes mellitus and FBS > 150mg/dL.
  • Severe medical illness or active infection that would impair the ability to receive gefitinib.
  • Pregnancy or breast feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01510990

Contacts
Contact: Sang-We Kim, M.D. 82-2-3010-3215 swkim@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Sang-We Kim, M.D.    82-2-3010-3215    swkim@amc.seoul.kr   
Principal Investigator: Sang-We Kim, M.D.         
Sponsors and Collaborators
Asan Medical Center
AstraZeneca
Investigators
Principal Investigator: Sang-We Kim, M.D. Asan Medical Center
  More Information

No publications provided

Responsible Party: Sang-We Kim, Principal Investigator, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01510990     History of Changes
Other Study ID Numbers: AMC 2011-0858
Study First Received: January 10, 2012
Last Updated: January 26, 2013
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
Non-small cell lung cancer
Gefitinib
FDG-PET

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014