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

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

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).

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer; Starting Pemetrexed Based Therapy; Unresectable Cancer
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

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:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.; 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".; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Sharyn I Katz, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: October 4, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Actual): May 12, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: LC130313