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Serial [18F]Thymidine (FLT)PET/CT as a Biomarker of Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

Primary Purpose

Non-small Cell Lung Cancer, Starting Pemetrexed Based Therapy, Unresectable Cancer

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Baseline 18F-thymidine (FLT) PET/CT

Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced tumor FLT "flare"

Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced changes in tumor proliferation

About this trial

This is an interventional diagnostic trial for Non-small Cell Lung Cancer

Eligibility Criteria

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

Inclusion Criteria:

Adult patients, at least 18 years of age
Histologically confirmed non-small cell lung cancer with at least one site of disease > 1 cm by at least one type of standard imaging (e.g. CT, chest x-ray, MRI)
Recommended to start systemic therapy which includes pemetrexed and a platinum-based agent.
Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.
Participants must be willing and able to comply with scheduled visits and imaging procedures in the opinion of the investigator or treating physician.

Exclusion Criteria:

Females who are pregnant or breast-feeding at the time of screening will not be eligible for this study. Female participants of child-bearing potential will have a urine pregnancy test at the time of the screening visit.
Patients with only a single site of primary lung cancer who have undergone or are recommended to undergo radiation therapy to that site will not be eligible, the inclusion of patients who may be undergoing radiation therapy to ancillary disease sites may be allowed to enter the study at the discretion of the PI if it is not felt to affect the ability to capture FLT information for at least one primary site of disease.
Patients who have received chemotherapy within 2 weeks of enrollment will be excluded from the study.
Patients who have undergone cancer surgery removing a significant portion of active disease, in the opinion of an investigator, within 2 months prior to study enrollment will be excluded.
Inability to tolerate imaging procedures in the opinion of the investigator or treating physician
Serious or unstable medical or psychological conditions that, in the opinion of the investigator would compromise the subject's safety or successful participation in the study.
Unwilling or unable to provide informed consent

Sites / Locations

Hospital of the University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients will be enrolled in a single arm of the study

Arm Description

All patients enrolled in the study will receive three 18F-thymidine (FLT) PET/CT scans at the following timepoints: before therapy, on the day of starting pemetrexed therapy (within 24 hours of starting pemetrexed) and at 2-4 weeks of starting pemetrexed therapy.

Outcomes

Primary Outcome Measures

Baseline 18F-thymidine PET/CT (FLT-PET/CT)

A baseline FLT-PET/CT will be performed prior to starting pemetrexed therapy. This scan will be used to compare to post therapy FLT-PET/CT in order to assess change in tumor accumulation of FLT.

Post-therapy 18F-thymidine PET/CT (FLT-PET/CT) to Assess Flare Response

FLT-PET/CT will be performed on the day of starting pemetrexed therapy. This scan will be used to compare to baseline FLT-PET/CT in order to assess change in tumor accumulation of FLT for evidence of an FLT "flare" response to pemetrexed therapy.

Post-therapy 18F-thymidine PET/CT (FLT-PET/CT) to Assess Tumor Proliferation Response

FLT-PET/CT will be performed at approximately 2-4 weeks following the start of pemetrexed therapy. This scan will be used to compare to baseline FLT-PET/CT in order to assess change in tumor accumulation of FLT for evidence of a tumor proliferation response to pemetrexed therapy.

Secondary Outcome Measures

Overall Survival

Overall survival from enrollment to 12 months from enrollment measured in months

Progression-free Survival

based on poor recruitment efforts subjects were unable to be analyzed

Full Information

NCT ID

NCT02274038

First Posted

October 4, 2014

Last Updated

May 11, 2021

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT02274038

Brief Title

Serial [18F]Thymidine (FLT)PET/CT as a Biomarker of Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

Official Title

Serial [18F]Fluorothymidine (FLT)PET/CT as a Biomarker of Therapeutic Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Terminated

Why Stopped

Poor Accrual

Study Start Date

March 2015 (Actual)

Primary Completion Date

July 2018 (Actual)

Study Completion Date

July 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

5. Study Description

Brief Summary

The investigators will test the hypothesis that positron emission tomography (PET) imaging with the imaging agent 18F-thymidine (FLT) can rapidly assess treatment response in patients with unresectable non-small cell lung cancer (NSCLC).

Detailed Description

We will test the hypothesis that positron emission tomography (PET) imaging with the imaging agent 18F-thymidine (FLT) can rapidly assess treatment response in patients with non-small cell lung cancer (NSCLC). In particular, we hypothesize that FLT-PET imaging will offer the potential of rapidly triaging therapy efficacy within hours to days following the start of therapy start by non-invasively monitoring metabolic changes in the tumor, rather than the conventional approach of waiting months for tumors to grow or shrink on computed tomography (CT). We propose two approaches to evaluate the potential of FLT-PET for assessment of response to therapy in NSCLC. In the first, we will exploit a specific effect (the FLT "flare") induced by pemetrexed, which is first-line chemotherapy for non-squamous NSCLC, to evaluate the utility of FLT-PET to assess successful response to pemetrexed (PEM) therapy within 24 hours. In the second approach, we will utilize FLT as a marker of cell proliferation, as has been done in other cancers, to determine whether chemotherapy has produced a decrease in tumor growth at 2 weeks after starting therapy. Since approximately 70% of patients will fail PEM-based therapy, an imaging technique that could reliably detect PEM efficacy in hours to days rather than months would save valuable time and allow for switch to a more effective therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer, Starting Pemetrexed Based Therapy, Unresectable Cancer

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

All patients will be enrolled in a single arm of the study

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Baseline 18F-thymidine (FLT) PET/CT

Intervention Description

FLT is a fluoro-labelled thymidine analog used as a radiotracer of tumor proliferation in PET/CT imaging. This baseline scan will be used to compare post-therapy FLT-PET/CT in order to assess change in tumor accumulation of FLT.

Intervention Type

Drug

Intervention Name(s)

Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced tumor FLT "flare"

Intervention Description

FLT is a fluoro-labelled thymidine analog used as a radiotracer of tumor proliferation in PET/CT imaging. This scan will be performed on the day of starting pemetrexed therapy (within 24hrs of starting pemetrexed) and used to compare to baseline FLT-PET/CT in order to assess change in tumor accumulation of FLT. The objective is to assess for early pemetrexed induced changes in tumor accumulation of FLT known as FLT "flare".

Intervention Type

Drug

Intervention Name(s)

Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced changes in tumor proliferation

Intervention Description

FLT is a fluoro-labelled thymidine analog used as a radiotracer of tumor proliferation in PET/CT imaging. This scan will be performed 2-4 weeks after starting pemetrexed therapy and used to compare to baseline FLT-PET/CT in order to assess change in tumor accumulation of FLT. The objective is to assess for pemetrexed induced changes in tumor accumulation of FLT as a surrogate measure of tumor proliferation.

Primary Outcome Measure Information:

Title

Baseline 18F-thymidine PET/CT (FLT-PET/CT)

Description

A baseline FLT-PET/CT will be performed prior to starting pemetrexed therapy. This scan will be used to compare to post therapy FLT-PET/CT in order to assess change in tumor accumulation of FLT.

Time Frame

Prior to starting pemetrexed based therapy

Title

Post-therapy 18F-thymidine PET/CT (FLT-PET/CT) to Assess Flare Response

Description

Time Frame

On the day that pemetrexed therapy is started

Title

Post-therapy 18F-thymidine PET/CT (FLT-PET/CT) to Assess Tumor Proliferation Response

Description

Time Frame

Approximately 2-4 weeks following start of pemetrexed therapy.

Secondary Outcome Measure Information:

Title

Overall Survival

Description

Overall survival from enrollment to 12 months from enrollment measured in months

Time Frame

1 year from study enrollment

Title

Progression-free Survival

Description

based on poor recruitment efforts subjects were unable to be analyzed

Time Frame

Within 1 year from study enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients, at least 18 years of age Histologically confirmed non-small cell lung cancer with at least one site of disease > 1 cm by at least one type of standard imaging (e.g. CT, chest x-ray, MRI) Recommended to start systemic therapy which includes pemetrexed and a platinum-based agent. Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures. Participants must be willing and able to comply with scheduled visits and imaging procedures in the opinion of the investigator or treating physician. Exclusion Criteria: Females who are pregnant or breast-feeding at the time of screening will not be eligible for this study. Female participants of child-bearing potential will have a urine pregnancy test at the time of the screening visit. Patients with only a single site of primary lung cancer who have undergone or are recommended to undergo radiation therapy to that site will not be eligible, the inclusion of patients who may be undergoing radiation therapy to ancillary disease sites may be allowed to enter the study at the discretion of the PI if it is not felt to affect the ability to capture FLT information for at least one primary site of disease. Patients who have received chemotherapy within 2 weeks of enrollment will be excluded from the study. Patients who have undergone cancer surgery removing a significant portion of active disease, in the opinion of an investigator, within 2 months prior to study enrollment will be excluded. Inability to tolerate imaging procedures in the opinion of the investigator or treating physician Serious or unstable medical or psychological conditions that, in the opinion of the investigator would compromise the subject's safety or successful participation in the study. Unwilling or unable to provide informed consent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sharyn I Katz, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Serial [18F]Thymidine (FLT)PET/CT as a Biomarker of Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

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