18F-Fluoromisonidazole and Fludeoxyglucose F 18 PET/CT Patients With Soft Tissue Sarcoma

Study Overview
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Brief Summary
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This phase II trial is studying 18F-fluoromisonidazole and fludeoxyglucose F 18 PET/CT scans to see how well they work in assessing oxygen in tumor tissue of patients with soft tissue sarcoma undergoing chemotherapy with or without radiation therapy. Using diagnostic procedures, such as 18F-fluoromisonidazole and fludeoxyglucose F 18 PET scan and CT scan, to find oxygen in tumor cells may help in planning cancer treatment. It may also help doctors predict how well a patient will respond to treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Evaluate the potential of 18F-fluoromisonidazole ([18F] FMISO) as a non-invasive indicator of tissue hypoxia to provide tumor-imaging data that correlates with tissue markers of hypoxia in patients with soft tissue sarcoma treated with neoadjuvant chemotherapy with or without radiotherapy. SECONDARY OBJECTIVES: I. Test [18F] FMISO tumor uptake as an independent predictor of patient outcome and if it provides additional predictive power over fludeoxyglucose F 18 PET scan. II. Test [18F] FMISO tumor uptake as a predictor of response in the subgroup of patients treated with radiotherapy and chemotherapy. III. Test the reproducibility of [18F] FMISO uptake in tumors by imaging the same patients on sequential days in a test-retest protocol. IV. Determine the relationship between hypoxia-related biomarkers (HIF1-a and VEGF), proliferation biomarkers (microvascular density, p53, and Ki-67), and regional [18F] FMISO uptake in tumor. OUTLINE: Patients undergo fludeoxyglucose F 18 [18F] FDG and 18F-fluoromisonidazole ([18F] FMISO) positron emission tomography (PET)/CT scans before starting neoadjuvant chemotherapy (without or without radiotherapy) and after completion of 4 courses of neoadjuvant therapy. NOTE: Some patients may undergo repeat [18F] FMISO PET/CT scan within 48 hours after the first [18F] FMISO scan to evaluate the variability (test-retest) of this imaging measurement. Blood samples are collected after completion of [18F] FMISO and [18F] FDG PET/CT scans for laboratory biomarker studies by IHC assays. Tumor samples from biopsy or surgery are also collected for biomarker studies. After completion of study procedures, patients are followed up periodically for 2 years.

Official Title
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A Phase 2 Study of Positron Emission Tomography Imaging With [18F]-Fluoromisonidazole (FMISO) and [18F]-Fluorodeoxyglucose (FDG) for Assessment of Tumor Hypoxia in Soft Tissue Sarcoma

Conditions
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Recurrent Adult Soft Tissue Sarcoma, Stage I Adult Soft Tissue Sarcoma, Stage II Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

Intervention / Treatment
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* Radiation: fludeoxyglucose F 18
* Other: 18F-fluoromisonidazole
* Procedure: positron emission tomography
* Procedure: computed tomography
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed intermediate- or high-grade soft tissue sarcoma Biopsy proven or highly suspicious primary or recurrent disease Tumor size ≥ 2 cm Scheduled to undergo neoadjuvant chemotherapy with or without radiotherapy Life expectancy ≥ 12 months Negative pregnancy test Willing to undergo PET scanning Willing to undergo possible urinary bladder catheterization (for patients with pelvic or proximal thigh tumors) Able to lie on the imaging table for up to 1.5 hours Weight ≤ 400 lbs Not pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (18F FDG and 18F FMISO PET/CT)<br>Patients undergo 18F FDG and 18F FMISO PET/CT scans before starting neoadjuvant chemotherapy (without or without radiotherapy) and after completion of 4 courses of neoadjuvant therapy. | Radiation: fludeoxyglucose F 18<br>* Undergo 18F FDG and 18F FMISO PET/CT scans<br>Other: 18F-fluoromisonidazole<br>* Undergo 18F FDG and 18F FMISO PET/CT scans<br>Procedure: positron emission tomography<br>* Undergo 18F FDG and 18F FMISO PET/CT scans<br>Procedure: computed tomography<br>* Undergo 18F FDG and 18F FMISO PET/CT scans<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline Hypoxic Volume (HV) | ANOVA and Kruskal-Wallis analysis will be performed across the different categories to look for significant associations. | Baseline and up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Multivariate Cox regression will be used. The outcome is binary and generalized linear models and logistic regression will be employed. | Up to 2 years | 
| Disease Free Survival | Multivariate Cox regression will be used. | From start of treatment to the follow-up review where recurrent disease is first detected, assessed up to 2 years | 
| Response to Radiation Therapy (XRT) by RECIST Criteria | Will be approached using multivariate logistic regression. | Up to 2 years |