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
Conditions
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.
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.
Interventions
RADIATIONfludeoxyglucose F 18
Undergo 18F FDG and 18F FMISO PET/CT scans
Undergo 18F FDG and 18F FMISO PET/CT scans
PROCEDUREpositron emission tomography
Undergo 18F FDG and 18F FMISO PET/CT scans
PROCEDUREcomputed tomography
Undergo 18F FDG and 18F FMISO PET/CT scans
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Response to Radiation Therapy (XRT) by RECIST Criteria | Up to 2 years | Will be approached using multivariate logistic regression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | Diagnostic (18F FDG and 18F FMISO PET/CT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 61 years |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Changes From Baseline Hypoxic Volume (HV)
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
Population: Study ended with 8 patients imaged at baseline and only 3 patients had 18F FMISO following therapy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diagnostic (18F FDG and 18F FMISO PET/CT) | Changes From Baseline Hypoxic Volume (HV) | 9.7 Cm^3 | Standard Deviation 11.7 |
Secondary
Disease Free Survival
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
Population: Study ended. No patients were assessed for disease free survival.No data were collected for this assessment
Secondary
Overall Survival
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
Population: Study ended. No patients were assessed for overall survival.No data were collected for this assessment.
Secondary
Response to Radiation Therapy (XRT) by RECIST Criteria
Will be approached using multivariate logistic regression.
Time frame: Up to 2 years
Population: Study ended. No patients were assessed for response to radiation therapy (XRT) by RECIST criteria. No data were collected for this assessment.