Fluorothymidine F-18 PET in Diagnosing Patients With Intermediate or High Grade Soft Tissue Sarcoma

A Pilot Study Investigating ¹⁸F-FLT-PET as a Marker of Response to Preoperative Radiotherapy in Soft Tissue Sarcoma

This pilot early phase I trial studies how well fluorothymidine F-18 positron emission tomography (PET) works in imaging patients with intermediate or high grade soft tissue sarcoma. Fluorothymidine F-18 PET may provide useful information about the tumor's response to treatment and may give the doctors early results that would better help to plan the post-surgical therapy.

Study Overview

• Status: Withdrawn
• Conditions: Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage IIA Adult Soft Tissue Sarcoma; Stage IIB Adult Soft Tissue Sarcoma; Stage IIC Adult Soft Tissue Sarcoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Fluorothymidine F-18; Procedure: Positron Emission Tomography

Detailed Description

PRIMARY OBJECTIVES:

I. To determine fluorothymidine F-18 (¹⁸F-FLT) uptake parameters before and after radiotherapy.

SECONDARY OBJECTIVES:

I. To correlate ¹⁸F-FLT uptake post-radiotherapy scan with pathologic response. II. To correlate levels the mitotic index in surgical specimens with the ¹⁸F-FLT uptake in post-radiation scans.

III. To correlate ¹⁸F-FLT uptake both pre- and post-radiotherapy with magnetic resonance imaging (MRI) enhancement both within and around the tumor.

TERTIARY OBJECTIVES:

I. To compare ¹⁸F-FLT uptake and fludeoxyglucose F-18 (FDG) uptake when FDG-PET-computed tomography (CT) is available, pre-radiation, post-radiation, or both.

II. To compare ¹⁸F-FLT uptake in post-radiation scans with local recurrences looking for spatial correlation.

OUTLINE:

Patients receive fluorothymidine F-18 intravenously (IV) over 1 minute and undergo PET scan over 60 minutes 21 or less days prior to standard of care radiation therapy and 14 or less days prior to the standard of care surgery.

After completion of study, patients are followed up for 2 years.

• Study Type: Interventional
• Phase: Early Phase 1

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:

• Participants must have histological evidence of an intermediate or high grade soft tissue sarcoma (STS) of any stage
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as >= 1 cm with CT scan or MRI
• Prior resection is allowed if there is measurable gross disease and the subject plans to have neoadjuvant radiotherapy followed by resection
• Eastern Cooperative Oncology Group (ECOG) performance status =< 4, Karnofsky performance status >= 40%
• Creatinine =< 3 x upper limit of normal (ULM)
• Blood urea nitrogen (BUN) =< 3 x ULN
• Participants should be willing and able to have both PET-CT scans
• Participants should be eligible for and plan to undergo neoadjuvant radiation therapy and should be seen by a radiation oncologist prior to beginning the study; radiation at an outside facility will be allowed
• Participants should be eligible for and plan to have resection with a surgeon specializing in STS at Oregon Health and Science University (OHSU) and should be seen by said surgeon prior to beginning the study
• Participants should have a life expectancy that is greater than the study duration
• Participants should be willing to use adequate contraception from the time of the first PET-CT scan to 2 months after radiotherapy finishes; should a woman become pregnant while participating in this study, she should inform her treating physician immediately
• Women with childbearing potential must have a negative pregnancy test before each PET-CT scan
• Participants should have the ability to understand and the willingness to sign a written informed consent document
• Participants must sign a study specific consent form prior to registration

Exclusion Criteria:

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or significant inflammation at treatment site or psychiatric illness/social situations that would limit compliance with study requirements or whose lab values do not meet the criteria above are excluded
• Pregnant women are excluded from this study
• Breast feeding women are excluded from this study
• Patients receiving chemotherapy during the course of radiation are excluded
• Patients whose weights exceed the tolerance of the table are excluded; the weight limit at OHSU is 450 pounds (lbs)

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: Diagnostic (fluorothymidine F-18 PET); Patients receive fluorothymidine F-18 IV over 1 minute and undergo PET scan over 60 minutes 21 or less days prior to standard of care radiation therapy and 14 or less days prior to the standard of care surgery.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Fluorothymidine F-18; Given IV; Other Names: fluorothymidine F 18; ¹⁸F-FLT; 3'-deoxy-3'-(¹⁸F) fluorothymidine; 3'-deoxy-3'-[¹⁸F]fluorothymidine; Procedure: Positron Emission Tomography; Undergo fluorothymidine F-18 PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; positron emission tomography scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fluorothymidine F-18 mean standardized uptake value (SUV) as response to therapy.	Measured by mean SUV where the response to therapy is Pathological Response Disease change in volume of tumor (in cm3) utilizing Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) with magnetic resonance imaging (MRI). Mean, median, standard deviation, and range will be reported for continuous variables. Box plot, histogram plot, and density plot may be used to graphically show the distribution of the continuous endpoints.	Pre (=< 21 days before radiation) and Post (=< 14 days before resection) radiation fluorothymidine F-18 positron emission tomography

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fluorothymidine F-18 peak SUV as response to therapy	Measured by peak SUV value where the response to therapy is Pathological Response Disease change in volume of tumor (in cm3) utilizing Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) with magnetic resonance imaging (MRI). Mean, median, standard deviation, and range will be reported for continuous variables. Box plot, histogram plot, and density plot may be used to graphically show the distribution of the continuous endpoints.	Pre (=< 21 days before radiation) and Post (=< 14 days before resection) radiation fluorothymidine F-18 positron emission tomography
Fluorothymidine F-18 mean SUV correlation with pathology mitotic index	Measured as Ki-67. Will assess the mitotic index of resection tissue. Spearman's correlation coefficient will be computed to assess the association between the mitotic index and fluorothymidine F-18 uptake parameters in post-radiation scans.	Post (=< 14 days before resection) radiation fluorothymidine F-18 positron emission tomography
Fluorothymidine F-18 peak SUV correlation with pathology mitotic index	Measured as Ki-67. Will assess the mitotic index of resection tissue. Spearman's correlation coefficient will be computed to assess the association between the mitotic index and fluorothymidine F-18 uptake parameters in post-radiation scans.	Post (=< 14 days before resection) radiation fluorothymidine F-18 positron emission tomography
Fluorothymidine F-18 peak SUV correlation with enhancement by MRI	Measured as Ki-67. Evaluated by the standard of care magnetic resonance imaging. Will assess the size and location of irregularly increased T2-weighted signal intensity. Descriptive statistical analysis will be conducted	Post (=< 14 days before resection) radiation fluorothymidine F-18 positron emission tomography
Volume of T2 enhanced MRI	Measured in (cm3).	Pre (=< 21 days before radiation) and Post (=< 14 days before resection) radiation fluorothymidine F-18 positron emission tomography

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Arthur Y Hung, MD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Anti-Infective Agents; Antiviral Agents; Alovudine
• Other Study ID Numbers: STUDY00016373 (Other Identifier: OHSU Knight Cancer Institute); P01CA042045 (U.S. NIH Grant/Contract); P30CA069533 (U.S. NIH Grant/Contract); NCI-2017-00833 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SOL-16169-LX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No