A Study of Changes in FDG- and FLT-PET Imaging in Patients With Non-Small Cell Lung Cancer Following Treatment With Erlotinib

Study Overview
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Brief Summary
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This is a single-arm, open-label, multicenter, international pilot study to evaluate changes that occur in 2-deoxy-2-[18F]fluoro-D-glucose (FDG)- and 3'-deoxy-3'-[18F]fluorothymidine(FLT)-PET (Positron Emission Tomography) imaging as a result of treatment with erlotinib in patients with recurrent or refractory non-small cell lung cancer (NSCLC). The study will enroll approximately 30 patients at approximately 4 sites in Australia and 2 sites in the United States.

Official Title
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Pilot Study of Changes in FDG- and FLT-PET Imaging in Patients With Non-Small Cell Lung Cancer Following Treatment With Erlotinib

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Other: 2-deoxy-2-[18F]fluoro-D-glucose (FDG)
* Other: 3'-deoxy-3'-[18F]fluorothymidine (FLT)
* Drug: erlotinib HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form(s) Histologically confirmed NSCLC Recurrent or progressive disease after receiving at least one chemotherapy regimen for advanced or metastatic NSCLC Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 Age ≥ 18 years Recovery from reversible acute effects of prior anti-cancer therapy (chemotherapy, radiotherapy, or investigational treatment) to NCI Common Toxicity Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 (excluding alopecia) Ability to comply with the study and follow-up procedures, including all specified imaging studies Ability to take oral medication Availability of archival diagnostic paraffin-embedded tumor tissue and willingness to provide sufficient tissue for testing for EGFR levels in tumor by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) Life expectancy ≥ 3 months Measurable disease on computed tomography (CT) At least one detectable lesion on FDG-PET scan and/or FLT-PET scan that is measurable on CT Use of an acceptable means of contraception (men and women of childbearing potential) or documentation of infertility Exclusion Criteria: Prior treatment with an investigational or marketed agent for the purpose of inhibiting epidermal growth factor receptor (EGFR) (including, but not limited to, erlotinib and gefitinib) Chemotherapy, radiotherapy, or investigational treatment within 14 days or within 5 half-lives of the active molecules in the chemotherapy or investigational treatment, whichever is longer, prior to study entry or from which patients have not yet recovered Inability to take oral medications, disease affecting gastrointestinal absorption, or prior surgical procedure affecting gastrointestinal absorption Uncontrolled diabetes Any unstable systemic disease (including active infection, unstable angina, congestive heart failure, myocardial infarction within 1 month prior to study entry, hepatic, renal, or metabolic disease) Pregnancy or lactation History of another malignancy in the past 2 years, unless the malignancy has been adequately treated, is currently not detectable, and is associated with a 5-year survival > 90% Claustrophobia Any other disease, condition, physical examination finding, or clinical laboratory finding which, in the opinion of the investigator, makes the patient inappropriate for the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Erlotinib 150 mg/day taken orally at approximately the same time of day with 200 mL (6-8 Ounces) of water on an empty stomach. Participants received Erlotinib for 1 year or until they developed progressive disease or intolerable toxicity. After 14 days and after 56 days of treatment with Erlotinib participants underwent FDG-PET and FLT-PET scans. | Other: 2-deoxy-2-[18F]fluoro-D-glucose (FDG)<br>* FDG prepared in sterile buffered solution for intravenous injection. Dosage was based on the participant's weight not to exceed 15 mCi (millicurie).<br>Other: 3'-deoxy-3'-[18F]fluorothymidine (FLT)<br>* FLT 7 mCi dose prepared in sterile buffered solution for intravenous injection.<br>Drug: erlotinib HCl<br>* Tablets taken orally 150 mg/day.<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) of Groups by FDG Response at Day 56 | PFS was defined as the time from the date of first erlotinib dose to disease progression or death, whichever occurs first. PFS was compared between patients with FDG-PET response and patients without FDG-PET response, independent of CT response (per RECIST 1.0) at Day 56 of treatment with erlotinib. Mean of the percent changes in maximal standard uptake values (mSUVmax) from FDG-PET scans was used to define FDG-PET response. Based on European Organization for Research on the Treatment of Cancer (EORTC) definitions, an objective FDG-PET response was defined an mSUVmax <-25%. | Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years | 
| PFS of Patients With FDG-PET Complete Response (CR)/Partial Response (PR) Versus FDG-PET Progressive Disease (PD) in Patients With Computed Tomography (CT) Stable Disease (SD) at Day 56 | PFS was defined as the time from the date of first erlotinib dose to disease progression or death, whichever occurs first. PFS was compared between patients with FDG-PET response (Complete /Partial Responses) and patients with FDG-PET progression, within the subset of patients who demonstrated stable disease on CT (per RECIST 1.0) at Day 56 of treatment with erlotinib. FDG-PET response; defined as a mSUVmax from FDG-PET scans of <-25% and FDG-PET disease progression; defined as a mSUVmax >+25% or the development of a new lesion with a mSUVmax above background not explained by another cause. | Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years | 
| Progression Free Survival of Groups by FLT Response at Day 56 | PFS was defined as the time from the date of first erlotinib dose to disease progression or death, whichever occurs first. PFS was compared between patients with FLT-PET response and patients without FLT-PET response, independent of CT response (per RECIST 1.0) at Day 56 of treatment with erlotinib. FLT-PET response was defined as a mSUVmax from FLT-PET scans <-25%. | Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years | 
| Progression Free Survival of Patients With FLT CR/PR Versus FLT PD in Patients With CT SD at Day 56 | PFS was defined as the time from the date of first erlotinib dose to disease progression or death, whichever occurs first. PFS was compared between patients with FLT-PET response and patients without FLT-PET response, independent of computed tomography (CT) response (per RECIST 1.0) at Day 56 of treatment with erlotinib. FLT-PET response was defined as a mSUVmax from FLT-PET scans <-25% and FLT-PET disease progression was defined as a mSUVmax from FLT-PET scans >+25% or the development of a new lesion with a mSUVmax above background not explained by another cause. | Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years | 
| Overall Survival of Groups by FDG Response at Day 56 | Overall survival (OS) was defined as the time from the date of first erlotinib dose to death. Overall survival (OS) was compared between patients with FDG-PET response and patients without FDG-PET response, independent of Response Evaluation Criteria in Solid Tumors (RECIST 1.0) computed tomography (CT) response at Day 56 of treatment with erlotinib. FDG-PET response was defined as a mSUVmax from FDG-PET scans <-25%. | From first erlotinib treatment to death, assessed up to 2 years | 
| Overall Survival of Patients With FDG CR/PR Versus FDG PD in Patients With CT SD at Day 56 | Overall survival (OS) was defined as the time from the date of first erlotinib dose to death. OS was compared between patients with FDG-PET response and patients with FDG-PET progression, within the subset of patients who demonstrated stable disease (SD) on CT (per RECIST 1.0) at Day 56 of treatment with erlotinib. FDG-PET response was defined as a mSUVmax from FDG-PET scans <-25% and FDG-PET disease progression was defined as a mSUVmax from FDG-PET scans >+25% or the development of a new lesion with a mSUVmax above background not explained by another cause. | From first erlotinib treatment to death, assessed up to 2 years | 
| Overall Survival of Groups by FLT Response at Day 56 | Overall survival (OS) was defined as the time from the date of first erlotinib dose to death. OS was compared between patients with FLT-PET response and patients without FLT-PET response, independent of CT response (per RECIST 1.0) at Day 56 of treatment with erlotinib. FLT-PET response was defined as a mSUVmax from FLT-PET scans <-25%. | From first erlotinib treatment to death, assessed up to 2 years | 
| Overall Survival of Patients With FLT CR/PR Versus FLT PD in Patients With CT SD at Day 56 | Overall survival (OS) was defined as the time from the date of first erlotinib dose to death. OS was compared between patients with FLT-PET response and patients with FLT-PET progression, within the subset of patients who demonstrated SD on CT (per RECIST 1.0) at Day 56 of treatment with erlotinib. FLT-PET response was defined as a mSUVmax from FLT-PET scans of <-25% and FLT-PET disease progression was defined as a mSUVmax from FLT-PET scans >+25% or the development of a new lesion with a mSUVmax above background not explained by another cause. | From first erlotinib treatment to death, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With FDG-PET Responses | In patients with computed tomography (CT)-stable disease (according to RECIST 1.0) at 56 days of erlotinib treatment, the percentage of patients who demonstrated FDG-PET responses after the initial 14 days and 56 days of erlotinib treatment. FDG-PET response was defined as a mSUVmax from FDG-PET scans <-25%. CT SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. | Day 14 and Day 56 | 
| Percentage of Patients With FLT-PET Responses | In patients with CT-stable disease (according to RECIST 1.0) at 56 days of erlotinib treatment, the percentage of patients who demonstrated FLT-PET responses after the initial 14 days and 56 days of erlotinib treatment. FLT-PET response was defined as a mSUVmax from FLT-PET scans <-25%. CT SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. | Day 14 and Day 56 | 
| FDG Response in Subgroups by CT Response at Day 56 | In patients with partial response or progressive disease on CT (per RECIST 1.0) after 56 days of erlotinib treatment, the percentage of patients who demonstrated FDG-PET responses on Day 56 defined as a mSUVmax from FDG-PET scans <-25%. CT Partial Response defined as a 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum of the LD. CT Progressive disease defined as a 20% increase in the sum of the longest diameter of target lesions taking as reference the smallest sum LD since treatment started or appearance of 1 or more new lesions. | Day 56 | 
| FLT Response in Subgroups by CT Response at Day 56 | In patients with partial response or progressive disease on CT (per RECIST 1.0) after 56 days of erlotinib treatment, the percentage of patients who demonstrated FLT-PET responses on Day 56 defined as a mSUVmax from FLT-PET scans <-25%. CT Partial Response defined as a 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum of the LD. CT Progressive disease defined as a 20% increase in the sum of the longest diameter of target lesions taking as reference the smallest sum LD since treatment started or appearance of 1 or more new lesions. | Day 56 | 
| Number of Participants With Adverse Events Due to FLT-PET Imaging | The number of participants who experienced an adverse event judged by the investigator to be related to FLT-PET. | From screening to Day 112 assessment visit or study discontinuation or termination, whichever is first. On visits after Day 112, only SAE were recorded. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Tarceva, Positron emission technology, PET, Computerized tomography, CT