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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
2-deoxy-2-[18F]fluoro-D-glucose (FDG)
3'-deoxy-3'-[18F]fluorothymidine (FLT)
erlotinib HCl
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring NSCLC, Tarceva, Positron emission technology, PET, Computerized tomography, CT

Eligibility Criteria

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

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Erlotinib

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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%.
    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.
    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%.
    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.
    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%.
    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.
    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%.
    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    March 26, 2007
    Last Updated
    March 2, 2017
    Sponsor
    Genentech, Inc.
    Collaborators
    Roche Pharma AG
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00453362
    Brief Title
    A Study of Changes in FDG- and FLT-PET Imaging in Patients With Non-Small Cell Lung Cancer Following Treatment With Erlotinib
    Official Title
    Pilot Study of Changes in FDG- and FLT-PET Imaging in Patients With Non-Small Cell Lung Cancer Following Treatment With Erlotinib
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2011
    Overall Recruitment Status
    Completed
    Study Start Date
    December 2006 (undefined)
    Primary Completion Date
    April 2010 (Actual)
    Study Completion Date
    April 23, 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Genentech, Inc.
    Collaborators
    Roche Pharma AG

    4. Oversight

    5. Study Description

    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.

    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
    NSCLC, Tarceva, Positron emission technology, PET, Computerized tomography, CT

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    88 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Erlotinib
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Other
    Intervention Name(s)
    2-deoxy-2-[18F]fluoro-D-glucose (FDG)
    Intervention Description
    FDG prepared in sterile buffered solution for intravenous injection. Dosage was based on the participant's weight not to exceed 15 mCi (millicurie).
    Intervention Type
    Other
    Intervention Name(s)
    3'-deoxy-3'-[18F]fluorothymidine (FLT)
    Intervention Description
    FLT 7 mCi dose prepared in sterile buffered solution for intravenous injection.
    Intervention Type
    Drug
    Intervention Name(s)
    erlotinib HCl
    Other Intervention Name(s)
    Tarceva
    Intervention Description
    Tablets taken orally 150 mg/day.
    Primary Outcome Measure Information:
    Title
    Progression Free Survival (PFS) of Groups by FDG Response at Day 56
    Description
    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 Frame
    Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years
    Title
    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
    Description
    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 Frame
    Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years
    Title
    Progression Free Survival of Groups by FLT Response at Day 56
    Description
    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 Frame
    Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years
    Title
    Progression Free Survival of Patients With FLT CR/PR Versus FLT PD in Patients With CT SD at Day 56
    Description
    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 Frame
    Time from first erlotinib treatment to disease progression on CT (per RECIST 1.0) or death, whichever occurs first, assessed up to 2 years
    Title
    Overall Survival of Groups by FDG Response at Day 56
    Description
    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%.
    Time Frame
    From first erlotinib treatment to death, assessed up to 2 years
    Title
    Overall Survival of Patients With FDG CR/PR Versus FDG PD in Patients With CT SD at Day 56
    Description
    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.
    Time Frame
    From first erlotinib treatment to death, assessed up to 2 years
    Title
    Overall Survival of Groups by FLT Response at Day 56
    Description
    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%.
    Time Frame
    From first erlotinib treatment to death, assessed up to 2 years
    Title
    Overall Survival of Patients With FLT CR/PR Versus FLT PD in Patients With CT SD at Day 56
    Description
    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.
    Time Frame
    From first erlotinib treatment to death, assessed up to 2 years
    Secondary Outcome Measure Information:
    Title
    Percentage of Patients With FDG-PET Responses
    Description
    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.
    Time Frame
    Day 14 and Day 56
    Title
    Percentage of Patients With FLT-PET Responses
    Description
    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.
    Time Frame
    Day 14 and Day 56
    Title
    FDG Response in Subgroups by CT Response at Day 56
    Description
    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.
    Time Frame
    Day 56
    Title
    FLT Response in Subgroups by CT Response at Day 56
    Description
    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.
    Time Frame
    Day 56
    Title
    Number of Participants With Adverse Events Due to FLT-PET Imaging
    Description
    The number of participants who experienced an adverse event judged by the investigator to be related to FLT-PET.
    Time Frame
    From screening to Day 112 assessment visit or study discontinuation or termination, whichever is first. On visits after Day 112, only SAE were recorded.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bernard Fine, M.D.
    Organizational Affiliation
    Genentech, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

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