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

Phase 1

Completed

Conditions: Non-Small Cell Lung Cancer

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

Registration Number: NCT00453362

Lead Sponsor: Genentech, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 88

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Erlotinib	3'-deoxy-3'-[18F]fluorothymidine (FLT)	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.
Erlotinib	2-deoxy-2-[18F]fluoro-D-glucose (FDG)	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.
Erlotinib	erlotinib HCl	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival of Patients With FDG CR/PR Versus FDG PD in Patients With CT SD at Day 56	From first erlotinib treatment to death, assessed up to 2 years	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.
Progression Free Survival of Patients With FLT CR/PR Versus FLT PD in Patients With CT SD at Day 56	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 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.
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	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 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.
Progression Free Survival of Groups by FLT Response at Day 56	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 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%.
Overall Survival of Groups by FDG Response at Day 56	From first erlotinib treatment to death, assessed up to 2 years	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%.
Overall Survival of Groups by FLT Response at Day 56	From first erlotinib treatment to death, assessed up to 2 years	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%.
Progression Free Survival (PFS) of Groups by FDG Response at Day 56	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 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%.
Overall Survival of Patients With FLT CR/PR Versus FLT PD in Patients With CT SD at Day 56	From first erlotinib treatment to death, assessed up to 2 years	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With FLT-PET Responses	Day 14 and Day 56	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.
Percentage of Patients With FDG-PET Responses	Day 14 and Day 56	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.
Number of Participants With Adverse Events Due to FLT-PET Imaging	From screening to Day 112 assessment visit or study discontinuation or termination, whichever is first. On visits after Day 112, only SAE were recorded.	The number of participants who experienced an adverse event judged by the investigator to be related to FLT-PET.
FDG Response in Subgroups by CT Response at Day 56	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.
FLT Response in Subgroups by CT Response at Day 56	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.