FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well PET scans using fluoromisonidazole F 18 and fludeoxyglucose F 18 work in finding oxygen in tumor cells of patients undergoing treatment for newly diagnosed stage 1B, stage II, stage II, or stage IV cervical cancer. Diagnostic procedures using positron emission tomography (PET scan), fluoromisonidazole F 18, and fludeoxyglucose F 18 to find oxygen in tumor cells may help doctors predict how patients will respond to treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Test the extent to which fluoromisonidazole F 18 ([^18F] FMISO) uptake predicts survival of patients undergoing therapy for newly diagnosed stage IB-IVB cervical cancer. SECONDARY OBJECTIVES: I. Test [^18F] FMISO tumor uptake as an independent predictor of response to therapy and that it provides additional predictive power over fludeoxyglucose F 18 ([^18F] FDG). II. Test [^18F] FMISO tumor uptake as a predictor of response in a subgroup of patients receiving radiotherapy. III. Test the relationship between [^18F] FMISO uptake in the primary tumor and the volume of the primary tumor estimated by CT scan. IV. Test the reproducibility of [^18F] FMISO uptake in tumors by imaging the same patients on sequential days in a test-retest protocol. V. Compare [^18F] FMISO PET or PET/CT scan with [^18F] FDG PET or PET/CT scan to test whether [^18F] FMISO is an independent predictor of treatment outcome. OUTLINE: Patients receive fluoromisonidazole F 18 ([^18F] FMISO) IV over 1 minute followed by PET scanning. Patients undergo a second [^18F] FMISO PET scan 4-8 weeks later. Patients who have not had a prior fludeoxyglucose F 18 ([^18F] FDG) PET scan as part of their routine clinical management undergo [^18F] FDG PET scanning at baseline. A subset of 10 patients undergo two [^18F] FMISO PET scans within a 48-hour period to evaluate the variability (test-retest) of this imaging measurement. Patients response to therapy is followed periodically until time to disease progression or 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 Cervical Cancer

Conditions
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Stage IVB Cervical Cancer, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Stage IB Cervical Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer, Stage IVA Cervical Cancer

Intervention / Treatment
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* Other: 18F-fluoromisonidazole
* Radiation: fluorodeoxyglucose F 18
* Procedure: positron emission tomography
* Other: tissue oxygen measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous cell or adenocarcinoma of the uterine cervix Clinical stage IB-IVB by FIGO criteria Size of the primary tumor ≥ 2 cm as assessed by CT scan Measurable disease Scheduled to undergo radiotherapy, chemotherapy, or combined multimodality management No prior cervical cancer diagnosis No known brain metastases ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%) Life expectancy > 12 months Not pregnant No nursing for 24 hours after fluoromisonidazole F 18 ([^18F] FMISO) PET scanning Negative pregnancy test Weight ≤ 400 lbs Sufficiently healthy to undergo cancer treatment Willing to undergo PET scanning with urinary bladder catheterization Leukocytes ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Total bilirubin normal AST/ALT ≤ 2.5 times normal Creatinine normal OR creatinine clearance ≥ 60 mL/min No serious medical co-morbidities that would preclude definitive local therapy No history of allergic reactions attributed to compounds of similar chemical or biologic composition to [^18F] FMISO No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness/social situations that would limit compliance with study requirements. No prior surgery or radiotherapy for cervical cancer Other concurrent investigational agents allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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 FMISO AND FDG PET<br>Patients receive ^18F FMISO IV over 1 minute followed by PET scanning. Patients undergo a second ^18F FMISO PET scan 4-8 weeks later. Patients who have not had a prior ^18F FDG PET scan as part of their routine clinical management undergo ^18F FDG PET scanning at baseline. | Other: 18F-fluoromisonidazole<br>* Undergo ^18F FMISO PET scan<br>* Other names: 18F-FMISO;Radiation: fluorodeoxyglucose F 18<br>* Undergo ^18F FDG PET scan<br>* Other names: FDG;Procedure: positron emission tomography<br>* Undergo ^18F-FMISO and ^18F FDG PET scan<br>* Other names: tomography, emission computed;Other: tissue oxygen measurement<br>* Undergo ^18 F FMISO PET and ^18F FDG PET<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Evaluate the value of pre-treatment FMISO results (T:B and HV) for all patients to predict the survival outcome variables. | For up to 2 years | 
| Disease-free Survival (DFS) | Evaluate the value of pre-treatment FMISO results (T:B and HV) for all patients to predict the disease free survival outcome variables. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship Between Hypoxia-related IHC Biomarkers and Regional FMISO Uptake in Tumor | The value of the biomarker by IHC analyses relates primarily to validating the information content of FMISO images. | Up to 2 years | 
| Relationship Between Ki67 and Regional FMISO Uptake in Tumor | The value of the biomarker Ki67 analyses relates primarily to validating the information content of FMISO images. | Up to 2 years | 
| Response to XRT Using RECIST | Response for the XRT is evaluated by the radiation oncologists as per standard clinical protocols | time to disease progression or 2 years following first FMISO scan |