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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01169350
• Collaborator: (none)
• Enrollment: 8
• Locations: 2
• Arm: 1
• Duration (Months): 42
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Radiation: fludeoxyglucose F 18; Other: 18F-fluoromisonidazole; Procedure: positron emission tomography; Procedure: computed tomography; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. Test [18F] FMISO tumor uptake as a predictor of response in the subgroup of patients treated with radiotherapy and chemotherapy.

3. Test the reproducibility of [18F] FMISO uptake in tumors by imaging the same patients on sequential days in a test-retest protocol.

4. 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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: 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
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

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.	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; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Changes From Baseline Hypoxic Volume (HV) [Baseline and up to 2 years]

   ANOVA and Kruskal-Wallis analysis will be performed across the different categories to look for significant associations.

Secondary Outcome Measures

1. Overall Survival [Up to 2 years]

   Multivariate Cox regression will be used. The outcome is binary and generalized linear models and logistic regression will be employed.

2. Disease Free Survival [From start of treatment to the follow-up review where recurrent disease is first detected, assessed up to 2 years]

   Multivariate Cox regression will be used.

3. Response to Radiation Therapy (XRT) by RECIST Criteria [Up to 2 years]

   Will be approached using multivariate logistic regression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023
2	University of Washington Medical Center	Seattle	Washington	United States	98195

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Janet Eary, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01169350
• Other Study ID Numbers: NCI-2011-01442; NCI-2011-01442; 8468; CDR0000665359; UW-8468; 6971; 8468; N01CM37008-9-0-0
• First Posted: Jul 26, 2010
• Last Update Posted: Nov 17, 2017
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Sarcoma; Fluorodeoxyglucose F18

Study Results

Participant Flow

Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	8
COMPLETED	3
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
Overall Participants	8
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 62.5%
>=65 years	3 37.5%
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Region of Enrollment (Count of Participants)
United States	8 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Study ended with 8 patients imaged at baseline and only 3 patients had 18F FMISO following therapy.

Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
Measure Participants	3
Mean (Standard Deviation) [Cm^3]	9.7 (11.7)

2. Secondary Outcome

Title	Overall Survival
Description	Multivariate Cox regression will be used. The outcome is binary and generalized linear models and logistic regression will be employed.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Study ended. No patients were assessed for overall survival.No data were collected for this assessment.

Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
Measure Participants	0

3. Secondary Outcome

Title	Disease Free Survival
Description	Multivariate Cox regression will be used.
Time Frame	From start of treatment to the follow-up review where recurrent disease is first detected, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

Study ended. No patients were assessed for disease free survival.No data were collected for this assessment

Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
Measure Participants	0

4. Secondary Outcome

Title	Response to Radiation Therapy (XRT) by RECIST Criteria
Description	Will be approached using multivariate logistic regression.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Study ended. No patients were assessed for response to radiation therapy (XRT) by RECIST criteria. No data were collected for this assessment.

Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected 24hr +/- 4 hours after each administration of [18F] FMISO.
Arm/Group Title	Diagnostic (18F FDG and 18F FMISO PET/CT)
Arm/Group Description	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. fludeoxyglucose F 18: Undergo 18F FDG and 18F FMISO PET/CT scans 18F-fluoromisonidazole: Undergo 18F FDG and 18F FMISO PET/CT scans positron emission tomography: Undergo 18F FDG and 18F FMISO PET/CT scans computed tomography: Undergo 18F FDG and 18F FMISO PET/CT scans laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Diagnostic (18F FDG and 18F FMISO PET/CT)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Diagnostic (18F FDG and 18F FMISO PET/CT)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Diagnostic (18F FDG and 18F FMISO PET/CT)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.