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

March 2, 2017 updated by: Genentech, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Erlotinib

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)
FDG prepared in sterile buffered solution for intravenous injection. Dosage was based on the participant's weight not to exceed 15 mCi (millicurie).
Other: 3'-deoxy-3'-[18F]fluorothymidine (FLT)
FLT 7 mCi dose prepared in sterile buffered solution for intravenous injection.
Drug: erlotinib HCl
Tablets taken orally 150 mg/day.
Other Names:
  • Tarceva

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) of Groups by FDG Response at Day 56
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

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
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

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
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

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
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

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
Time Frame: 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%.
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
Time Frame: 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.
From first erlotinib treatment to death, assessed up to 2 years
Overall Survival of Groups by FLT Response at Day 56
Time Frame: 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%.
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
Time Frame: 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.
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
Time Frame: 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.
Day 14 and Day 56
Percentage of Patients With FLT-PET Responses
Time Frame: 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.
Day 14 and Day 56
FDG Response in Subgroups by CT Response at Day 56
Time Frame: 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
Time Frame: 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
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genentech, Inc.

Collaborators

Roche Pharma AG

Investigators

  • Study Director: Bernard Fine, M.D., Genentech, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 23, 2010

Study Registration Dates

First Submitted

March 26, 2007

First Submitted That Met QC Criteria

March 26, 2007

First Posted (Estimate)

March 28, 2007

Study Record Updates

Last Update Posted (Actual)

March 31, 2017

Last Update Submitted That Met QC Criteria

March 2, 2017

Last Verified

October 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSI3926g
  • ML20773

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe