An Imaging Agent (Fluorodopa F 18) With Positron Emission Tomography/Magnetic Resonance Imaging for Assessing Treatment Response in Patients With High-Grade Soft Tissue Sarcomas

Utility of 18F-DOPA PET/MRI Metrics as a Biomarker for Treatment Response Assessment in Sarcoma Patients: A Pilot Study

This study evaluates the use of a new imaging agent called fluorodopa F 18 (18F-DOPA) with positron emission tomography/magnetic resonance imaging (PET/MRI) for assessing treatment response in patients undergoing standard of care radiation therapy and/or surgery for high-grade soft tissue sarcomas that are new or that have come back (recurrent). Though there have been improvements in treatment options for soft tissue sarcomas, there is currently a need for a non-invasive way to determine a patient's potential benefit from receiving one of these treatments. 18F-DOPA with PET/MRI allows a patient's tumor to be visualized and their response to a given treatment assessed.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma; Recurrent Soft Tissue Sarcoma; Resectable Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Fluorodopa F 18; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Procedure: Surgical Procedure

Detailed Description

PRIMARY OBJECTIVE:

I. Determine the correlation between 18F-DOPA PET/MRI quantitative metrics after neoadjuvant treatment (pre-surgery) with percent tumor necrosis.

SECONDARY OBJECTIVE:

I. Compare the changes in 18F-DOPA PET/MRI quantitative metrics between baseline (before radiotherapy [RT]) and after RT, but before surgery with percent tumor necrosis.

OUTLINE:

Patients receive 18F-DOPA intravenously (IV) and undergo PET/MRI over 60 minutes before standard of care radiotherapy and/or before standard of care surgery.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trial Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Deanna H. Pafundi, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients planning to receive surgery for high-grade soft tissue sarcoma.

Description

Inclusion Criteria:

• PRE-ELIGIBILITY - INCLUSION CRITERIA:
• Age >= 18 years
• Histological confirmation of newly diagnosed soft tissue sarcoma or recurrent soft tissue sarcoma >= 1-year post-treatment
• Tumors > 1 cm in diameter in largest dimension located midline within the torso or neck, retroperitoneal, or lower extremities
• Operable sarcoma, planning to receive surgery with or without neoadjuvant RT/chemotherapy at Mayo Clinic Florida. Systemic therapy is allowed during radiotherapy
• Provide informed written consent
• Willingness to participate in mandatory imaging studies at Mayo Clinic Florida

Exclusion Criteria:

• POST-ELIGIBILITY - EXCLUSION CRITERIA:
• 18F-DOPA PET uptake deemed as unacceptable for quantitative assessment
• Unable to undergo an 18F-DOPA PET/MRI scan due to standard MRI restrictions, such as for those with certain implanted devices, those who cannot fit inside the bore, or those with severe claustrophobia

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Observational (18F-DOPA PET/MRI); Patients receive 18F-DOPA IV and undergo PET/MRI over 60 minutes before standard of care radiotherapy and/or before standard of care surgery.

Drug: Fluorodopa F 18; Given IV; Other Names: (18F)FDOPA; 18F-DOPA; 18F-FDOPA; 3-(2-Fluoro-(sup 18)F-4,5-dihydroxyphenyl)-L-alanine; 6-(18F)Fluoro-L-DOPA; Fluorine F 18 Fluorodopa; Fluorine-18-fluoro-L-DOPA; Fluorodopa (18F); FLUORODOPA F-18; L-6-(18F)Fluoro-DOPA; Procedure: Magnetic Resonance Imaging; Undergo PET/MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Undergo PET/MRI; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Radiation: Radiation Therapy; Receive standard of care radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Procedure: Surgical Procedure; Undergo standard of care surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorodopa F 18 (18F-DOPA) positron emission tomography (PET)	Correlated with pathologic response. The correlation between imaging measures and pathologic response will be evaluated using a logistic regression model for each one of the four imaging modalities separately. For each subject, 12-18 measures will be taken, and therefore, an exchangeable correlation structure will be used to model the correlation among the measures from the same patient. Giving the exploratory nature of the study, will not adjust for the multiple comparisons. Pathologic responses and imaging measurements will be summarized using point estimates, and 95% confidence interval as well, for each of the four imaging modalities.	Post-radiation therapy (RT) up to 28 days.
Change in 18F-DOPA PET activity	Pre-radiation therapy and post-radiation therapy 18F-DOPA PET activity will be correlated with pathologic response. The correlation between imaging measures and pathologic response will be evaluated using a logistic regression model for each one of the four imaging modalities separately. For each subject, 12-18 measures will be taken, and therefore, an exchangeable correlation structure will be used to model the correlation among the measures from the same patient. Giving the exploratory nature of the study, will not adjust for the multiple comparisons. Pathologic responses and imaging measurements will be summarized using point estimates, and 95% confidence interval as well, for each of the four imaging modalities.	Pre- to post-Rt up to 28 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic response	Pathologic evaluation of resected specimens by an expert pathologist will be the gold standard for tumor diagnosis and treatment response assessment in this study. Following definitive surgery, the tumor should be examined to determine pathologic response. Since the effect of the preoperative RT may not be uniform throughout the tumor, adequate sampling is required to grade the pathologic response accurately. Tumor's pathologic response will be performed utilizing the grading system below as a guideline: grade I is defined as the percentage of necrosis less than 50%, grade II is defined as the 50%-89% necrosis in the sample, grade III is defined as 90% - 99% necrosis and grade IV is defined as 100% necrosis. The pathological endpoint is defined as the indicator of whether the percentage of necrosis is > 90%.	Through study completion, an average of 1 year
Imaging Endpoint Standardized uptake value (SUV) mean	Imaging endpoints include SUV uptake value mean characteristic. Five patients will be enrolled before RT for additional PET scan for comparison of pre-RT and post-RT SUV metrics, correlated with pathology after surgery, for evaluation of 18F-DOPA PET as a marker for response assessment.	Up to 3 years
Imaging Endpoint SUV maximum	Imaging endpoints include SUV maximum characteristic. Five patients will be enrolled before RT for additional PET scan for comparison of pre-RT and post-RT SUV metrics, correlated with pathology after surgery, for evaluation of 18F-DOPA PET as a marker for response assessment.	Up to 3 years
Imaging Endpoint Tumor-to-normal SUV	Imaging endpoints include tumor to normal SUV characteristic. Five patients will be enrolled before RT for additional PET scan for comparison of pre-RT and post-RT SUV metrics, correlated with pathology after surgery, for evaluation of 18F-DOPA PET as a marker for response assessment.	Up to 3 years
Imaging Endpoint Total metabolic tumor volume	Imaging endpoints include total metabolic tumor volume characteristic. Five patients will be enrolled before RT for additional PET scan for comparison of pre-RT and post-RT SUV metrics, correlated with pathology after surgery, for evaluation of 18F-DOPA PET as a marker for response assessment.	Up to 3 years
Imaging Endpoint Total tumor glycolysis	Imaging endpoints include total tumor glycolysis characteristic. Five patients will be enrolled before RT for additional PET scan for comparison of pre-RT and post-RT SUV metrics, correlated with pathology after surgery, for evaluation of 18F-DOPA PET as a marker for response assessment.	Up to 3 years
Imaging Endpoint Tumor histogram characteristics	Imaging endpoints include tumor histogram characteristic. Five patients will be enrolled before RT for additional PET scan for comparison of pre-RT and post-RT SUV metrics, correlated with pathology after surgery, for evaluation of 18F-DOPA PET as a marker for response assessment.	Up to 3 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Deanna H. Pafundi, Ph.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: September 19, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agents; Cariostatic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Fluorides; Levodopa
• Other Study ID Numbers: MC220702; 21-005244 (Other Identifier: Mayo Clinic Institutional Review Board); NCI-2022-04924 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

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