Clinical trial NCT00775268: 18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma
Official title: A Pilot Study of 18F Fluorothymidine (FLT) PET/CT in Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: 18F-Fluorothymidine
PET/CT
FLT
Lymphoma
FDG
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2008-10-20
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Background:

* Positron emission tomography (PET) uses radioactive substances called radiotracers to locate areas of cancer in the body. For this test, the patient is given an injection of the radiotracer and lies in a large donut-shaped scanner that detects where in the body the radioactivity accumulates. Computed tomography (CT) scans use low dose x-rays that help to better localize where the radioactive tracer is concentrating. PET/CT scans are usually done in lymphoma patients before treatment starts and at the end of treatment to evaluate the response to therapy.
* PET scans typically use a sugar-like radioactive tracer called fluorodeoxyglucose (FDG) and low-dose x-rays. Sometimes, however, FDG PET scans show what looks like active disease and presence of a mass after chemotherapy even when there are no live cancer cells. Doctors have particular problems in evaluating response to treatment when this happens because they can't tell if the mass is active cancer or just dead tumor cells.
* An experimental radiotracer called 18F- Fluorothymidine (FLT) has high uptake in active tumor cells and may be better able to evaluate treatment response.

Objectives:

- To test the use of FLT PET/CT imaging in assessing treatment response in patients with lymphoma.

Eligibility:

- Patients 18 years of age or older who are enrolled in a lymphoma therapy study at the National Institutes of Health (NIH) Clinical Center or in the Cancer and Leukemia Group B (CALGB) 50330 study at another location.

Design:

- There are two arms in this study:

* The first arm evaluates FLT as an early predictor of tumor response to therapy. Patients are imaged with FLT and FDG PET before starting treatment, following two cycles of therapy and after treatment ends.
* The second arm evaluates the ability of FLT to distinguish if a mass that remains after treatment has viable cancer or dead tissue. Patients who have completed treatment and in whom FDG PET shows a remaining tumor mass are imaged with FLT PET. Following the scan, the tumor is biopsied for verification.

Detailed description: Background:

* 3-deoxy-3-18F-fluorothymidine (FLT) positron emission tomography (FLT PET)/Compute tomography (CT) has been shown to correlate with the rate of cellular/tumor proliferation.
* The Imaging Subcommittee of the International Harmonization Project in Lymphoma recommends performing fluorodeoxyglucose (FDG) positron emission tomography (PET) at least 3 weeks, and preferably 6-8 weeks after chemotherapy or chemoimmunotherapy and 8-12 weeks after radiation or chemoradiation therapy due to high FDG accumulation in inflammatory tissues.
* FLT uptake in inflammatory lesions is less prominent than FDG and it is likely that FLT PET/CT can better differentiate inflammation from tumor.
* FLT PET/CT imaging is expected to better differentiate between treatment induced inflammation and malignancy and should enable early prediction of therapeutic response.
* FLT PET/CT imaging is expected to differentiate between residual inflammatory residual masses from residual malignancy and therefore guide appropriate treatment.

Primary Objectives:

* To estimate the diagnostic accuracy of FLT PET/CT as an early indicator of complete response to therapy in B and T cell lymphoma.
* To estimate the diagnostic accuracy of FLT PET/CT in the evaluation of residual masses after therapy.

Eligibility:

* Participant must be enrolled in a lymphoma therapy study at the National Institutes of Health (NIH) Clinical Center OR be enrolled in the CALGB 50303 study at another site OR undergoing a new course of treatment of lymphoma at another facility. The National Cancer Institute (NCI) Laboratory of Pathology will confirm diagnosis for subjects enrolled at all CALGB study sites.
* Participants must have a clinical course consistent with lymphoma and have available documentation of lymphoma from either the NCI or from an outside pathology laboratory.
* Subjects enrolling in the early response arm must undergo baseline FLT PET prior to receiving a new course of lymphoma therapy.
* Subjects enrolling in the residual mass evaluation arm can be enrolled at the time the FDG avid residual mass is discovered (i.e. no pre-therapy FLT image is required).
* Subjects can enroll in both arms of the study.
* Participant must be 18 years or older.
* Eastern Cooperative Oncology Group (ECOG) Performance score of 0 or 1.
* Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) less than 5 times upper limit of normal (ULN).
* bilirubin less than or equal to 2 times ULN.

Design:

There are 2 arms in this study

* The first arm will assess FLT as an early predictor of tumor response to therapy (treatment naive or recurrent disease). Subjects are imaged with FLT and FDG PET pre-therapy, following 2 cycles of therapy and post therapy.
* The second arm will assess lymphoma patients with FDG PET positive residual mass. Subjects are imaged with FLT PET prior to standard of care biopsy of residual mass. If initial FDG PET data is not available in Digital Imaging and Communications in Medicine (DICOM) format or is of suboptimal image quality, a repeat FDG PET/CT at the study site may be required.

  * We will accrue 70 participants (40 in the early response arm and 30 in the residual mass arm) to this study.

Eligibility criteria: * INCLUSION CRITERIA:

Participant must be enrolled in a lymphoma therapy study at the National Institutes of Health (NIH) Clinical Center OR be enrolled in the Cancer and Leukemia Group B (CALGB) 50303 study at another site OR undergoing a new course of treatment of lymphoma at another facility.

Participants must have a clinical course consistent with lymphoma and have available documentation of lymphoma from either the National Cancer Institute (NCI) or from an outside pathology laboratory.

Participant must be 18 years or older.

Eastern Cooperative Oncology Group (ECOG) Performance score of 0 or 1.

Ability to provide informed consent. All patients must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed.

For subjects enrolling in early response arm

* Must be enrolled in CALGB 50303 or a lymphoma therapy study at the NIH Clinical Center or undergoing a new course of treatment of lymphoma at another facility
* Must not have begun lymphoma therapy for this tumor occurrence/ relapse
* Prior completed therapy does NOT affect eligibility

For subjects enrolling in the residual FDG avid mass arm

* Must have a residual (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) positive mass greater than equal to 1cm, with uptake greater than that of mediastinal blood pool.
* Participant will undergo a repeat FDG PET/CT scan if the original FDG/PET imaging performed at an outside institution is not of adequate imaging quality for subjects enrolling in the residual FDG mass arm.

EXCLUSION CRITERIA:

Known allergy to fluorothymidine.

Participants for whom enrollment would significantly delay (greater than 2 weeks) the scheduled standard of care therapy.

Participants with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results are excluded.

Participants with severe claustrophobia not relieved by oral anxiolytic medication or patients weighing greater than 136 kg (weight limit for scanner table).

Other medical conditions deemed by the Principal Investigator (PI) or associates to make the patient ineligible for protocol procedures.

Primary outcomes:
measure: Number of Participants With the Presence/Absence of Abnormal 18F- Fluorothymidine (FLT) Uptake, and Positive/Negative Biopsy
timeFrame: Up to 3.5 years
Secondary outcomes:
measure: 18F- Fluorothymidine (FLT) Uptake Within the Tumor(s) Between Baseline vs Completion of Therapy Scans
timeFrame: up to 4.5 years
measure: Tumor(s) Maximum Standard Uptake Value (SUVmax) at Baseline Scan and SUVmax After Completion Scan in Responders and Non-responders' Patients
timeFrame: up to 4.5 years
measure: Tumor Uptake With Fluorothymidine (FLT) - Maximum Standard Uptake Value (SUVmax)
timeFrame: Up to 4.5 years
measure: 18F-fluorodeoxyglucose (18FDG) Standardized Uptake Values (SUV) Estimated Maximum and Tumor: Blood Pool Ratio at 1-hour Post-injection
timeFrame: up to 3.5 years
measure: 3'-Deoxy-3'-[18F]-Fluorothymidine (FLT) Dynamic Influx Parameter (Ki) Standardized Uptake Values (SUV) Estimated Maximum at 1- and 2-hours Post-injection
timeFrame: up to 3.5 years
measure: Tumor(s) Maximum Standard Uptake Value (SUVmax) at Baseline and at Mid-treatment (Post-2 Cycles) Scan
timeFrame: Up to 4.5 years
measure: Time to Progression
timeFrame: up to 4.5 years
measure: 18F- Fluorothymidine (FLT) Uptake, Positron-emission Tomography (PET) Standard Uptake Value (SUV)Max in Malignant Residual Tumors Versus Benign Lesions After Therapy
timeFrame: up to 4.5 years
Other outcomes:
measure: Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
timeFrame: Date treatment consent signed to date off study, approximately 4 years, 7 months and 9 days.
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Medical Center
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Esther Mena, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Thomas J, de Groot T, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G. Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Sep;13(9):1356-63. doi: 10.1093/annonc/mdf256.
citation: Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.