Clinical trial NCT02274038: 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
Overall status: TERMINATED
Phase: NA
Conditions: Non-small Cell Lung Cancer
Starting Pemetrexed Based Therapy
Unresectable Cancer
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2014-10-24
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Baseline 18F-thymidine PET/CT (FLT-PET/CT)
timeFrame: Prior to starting pemetrexed based therapy
measure: Post-therapy 18F-thymidine PET/CT (FLT-PET/CT) to Assess Flare Response
timeFrame: On the day that pemetrexed therapy is started
measure: Post-therapy 18F-thymidine PET/CT (FLT-PET/CT) to Assess Tumor Proliferation Response
timeFrame: Approximately 2-4 weeks following start of pemetrexed therapy.
Secondary outcomes:
measure: Overall Survival
timeFrame: 1 year from study enrollment
measure: Progression-free Survival
timeFrame: Within 1 year from study enrollment
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Sharyn I Katz, MD
role: PRINCIPAL_INVESTIGATOR
References: