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

NCT00453362 | Completed Phase 1 Results

• 2 other identifiers: OSI3926gML20773
• Study Type: interventional
• Target: 88
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (5)

• Percentage of Patients With FDG-PET Responses

  Day 14 and Day 56

• Percentage of Patients With FLT-PET Responses

  Day 14 and Day 56

• FDG Response in Subgroups by CT Response at Day 56

  Day 56

• FLT Response in Subgroups by CT Response at Day 56

  Day 56

• 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.

Study Arms (1)

Erlotinib

EXPERIMENTAL

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); Other: 3'-deoxy-3'-[18F]fluorothymidine (FLT); Drug: erlotinib HCl

Interventions

2-deoxy-2-[18F]fluoro-D-glucose (FDG) OTHER

FDG prepared in sterile buffered solution for intravenous injection. Dosage was based on the participant's weight not to exceed 15 mCi (millicurie).

Erlotinib

3'-deoxy-3'-[18F]fluorothymidine (FLT) OTHER

FLT 7 mCi dose prepared in sterile buffered solution for intravenous injection.

Erlotinib

erlotinib HCl DRUG

Tablets taken orally 150 mg/day.

Also known as: Tarceva

Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead
• Roche Pharma AG: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Fluorodeoxyglucose F18; alovudine; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• Bernard Fine, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2007
• First Posted: March 28, 2007
• Study Start: December 1, 2006
• Primary Completion: April 1, 2010
• Study Completion: April 23, 2010
• Last Updated: March 31, 2017
• Results First Posted: October 3, 2011

Record last verified: 2011-10