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First Line Gefitinib by FDG-PET Metabolic Response

Primary Purpose

Non-small Cell Lung Cancer

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Gefitinib

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Non-small cell lung cancer, Gefitinib, FDG-PET

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Asan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gefitinib

Arm Description

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.

Outcomes

Primary Outcome Measures

Objective Response rate

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

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.

Full Information

NCT ID

NCT01510990

First Posted

January 10, 2012

Last Updated

January 26, 2013

Sponsor

Asan Medical Center

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01510990

Brief Title

First Line Gefitinib by FDG-PET Metabolic Response

Official Title

First Line Gefitinib Treatment for Advanced Non-small Cell Lung Cancer (NSCLC) by the FDG-PET Metabolic Response

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Unknown status

Study Start Date

April 2012 (undefined)

Primary Completion Date

June 2013 (Anticipated)

Study Completion Date

November 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Asan Medical Center

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer, Gefitinib, FDG-PET

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gefitinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gefitinib

Other Intervention Name(s)

Iressa

Intervention Description

gefitinib 250mg/day daily

Primary Outcome Measure Information:

Title

Objective Response rate

Description

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.

Time Frame

one year

Secondary Outcome Measure Information:

Title

Objective response rate by EGFR mutational status

Description

Time Frame

One year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sang-We Kim, M.D.

Phone

82-2-3010-3215

swkim@amc.seoul.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sang-We Kim, M.D.

Organizational Affiliation

Asan Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Asan Medical Center

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sang-We Kim, M.D.

Phone

82-2-3010-3215

swkim@amc.seoul.kr

First Name & Middle Initial & Last Name & Degree

Sang-We Kim, M.D.

12. IPD Sharing Statement

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First Line Gefitinib by FDG-PET Metabolic Response

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