FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

Phase 2

Completed

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

Interventions: Other: 18F-fluoromisonidazole
Radiation: fluorodeoxyglucose F 18
Procedure: positron emission tomography
Other: tissue oxygen measurement

Registration Number: NCT00559377

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 16

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic FMISO AND FDG PET	18F-fluoromisonidazole	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.
Diagnostic FMISO AND FDG PET	fluorodeoxyglucose F 18	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.
Diagnostic FMISO AND FDG PET	positron emission tomography	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.
Diagnostic FMISO AND FDG PET	tissue oxygen measurement	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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