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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Baseline 18F-thymidine (FLT) PET/CT
* Drug: Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced tumor FLT flare
* Drug: Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced changes in tumor proliferation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients will be enrolled in a single arm of the study<br>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. | Drug: Baseline 18F-thymidine (FLT) PET/CT<br>* 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.<br>Drug: Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced tumor FLT flare<br>* 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.<br>Drug: Post-therapy 18F-thymidine (FLT) PET/CT to assess for pemetrexed induced changes in tumor proliferation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Prior to starting pemetrexed based therapy | 
| 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. | On the day that pemetrexed therapy is started | 
| 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. | Approximately 2-4 weeks following start of pemetrexed therapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival from enrollment to 12 months from enrollment measured in months | 1 year from study enrollment | 
| Progression-free Survival | based on poor recruitment efforts subjects were unable to be analyzed | Within 1 year from study enrollment |