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

NCT ID: NCT02274038

Last Updated: 2021-05-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2018-07-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Baseline 18F-thymidine (FLT) PET/CT

Intervention Type: DRUG

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.

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

Intervention Type: DRUG

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".

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

Intervention Type: DRUG

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.

Interventions

Baseline 18F-thymidine (FLT) PET/CT

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

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

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

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

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult patients, at least 18 years of age

2. 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)

3. Recommended to start systemic therapy which includes pemetrexed and a platinum-based agent.

4. 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.

5. 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

1. 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.

2. 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.

3. Patients who have received chemotherapy within 2 weeks of enrollment will be excluded from the study.

4. 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.

5. Inability to tolerate imaging procedures in the opinion of the investigator or treating physician

6. 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.

7. Unwilling or unable to provide informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sharyn I Katz, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

LC130313

Identifier Type: -

Identifier Source: org_study_id