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

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

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Radiation: fludeoxyglucose F 18; Other: 18F-fluoromisonidazole; Procedure: positron emission tomography; Procedure: computed tomography

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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 (18F FDG and 18F FMISO PET/CT); 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.	Other: laboratory biomarker analysis; Correlative studies; Radiation: fludeoxyglucose F 18; Undergo 18F FDG and 18F FMISO PET/CT scans; Other: 18F-fluoromisonidazole; Undergo 18F FDG and 18F FMISO PET/CT scans; Procedure: positron emission tomography; Undergo 18F FDG and 18F FMISO PET/CT scans; Procedure: computed tomography; Undergo 18F FDG and 18F FMISO PET/CT scans

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Janet Eary, University of Washington

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: July 23, 2010
• First Submitted That Met QC Criteria: July 23, 2010
• First Posted (Estimate): July 26, 2010

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: NCI-2011-01442 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 6971 (University of Washington Medical Center); 8468 (Other Identifier: CTEP); CDR0000665359; UW-8468; N01CM37008-9-0-0 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No