First Line Gefitinib by FDG-PET Metabolic Response

NCT ID: NCT01510990

Last Updated: 2013-01-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2015-11-30

Brief Summary

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.

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Gefitinib

Intervention Type: DRUG

gefitinib 250mg/day daily

Interventions

Gefitinib

gefitinib 250mg/day daily

Intervention Type: DRUG

Other Intervention Names

Iressa

Eligibility 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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sang-We Kim

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sang-We Kim, M.D.

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

Asan Medical Center

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Sang-We Kim, M.D.

Role: CONTACT

swkim@amc.seoul.kr

82-2-3010-3215

Facility Contacts

Sang-We Kim, M.D.

Role: primary

swkim@amc.seoul.kr

82-2-3010-3215

Other Identifiers

AMC 2011-0858

Identifier Type: -

Identifier Source: org_study_id