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, Stage IVB Cervical Cancer
Conditions
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.
Interventions
Undergo \^18F FMISO PET scan
RADIATIONfluorodeoxyglucose F 18
Undergo \^18F FDG PET scan
PROCEDUREpositron emission tomography
Undergo \^18F-FMISO and \^18F FDG PET scan
Undergo \^18 F FMISO PET and \^18F FDG PET
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients Patients receive \^18F FMISO IV followed by PET scanning. Patients undergo a second \^18F FMISO PET scan 4-8 weeks later. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Gender Female | 16 Participants |
| Gender Male | 0 Participants |
| Region of Enrollment United States | 16 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
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.
Time frame: Up to 2 years
Population: Of the 13 patients analyzed for disease-free survival, 10 remained disease-free throughout the 2 year follow up. For 3 patients, we could determine overall survival, but could not confirm whether or not they were disease-free.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Year Overall Survival | Disease-free Survival (DFS) | 10 participants disease-free after 2 years |
Comparison: This outcome is for comparison of FMISO Hypoxic Volume to disease-free survivalp-value: 0.58Regression, Cox
Comparison: This outcome is for comarison of FMISO T:Bmax to progression-free survivalp-value: 0.98Regression, Cox
Primary
Overall Survival (OS)
Evaluate the value of pre-treatment FMISO results (T:B and HV) for all patients to predict the survival outcome variables.
Time frame: For up to 2 years
Population: 1 patient has been lost to follow up for survival measures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Year Overall Survival | Overall Survival (OS) | 11 participants still alive after 2 years |
Comparison: This outcome is for comparing FMISO Hypoxic Volume to overall survivalp-value: 0.42Regression, Cox
Comparison: This outcome is for comparing FMISO T:Bmax to overall survivalp-value: 0.87Regression, Cox
Secondary
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.
Time frame: Up to 2 years
Population: 11 tissue samples with Hif1, VEGF, p53 and EGFR IHC values were compared to FMISO uptake.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 2 Year Overall Survival | Relationship Between Hypoxia-related IHC Biomarkers and Regional FMISO Uptake in Tumor | Hif1 | 5 units on a scale 0=low, 8=high |
| 2 Year Overall Survival | Relationship Between Hypoxia-related IHC Biomarkers and Regional FMISO Uptake in Tumor | VEGF | 5 units on a scale 0=low, 8=high |
| 2 Year Overall Survival | Relationship Between Hypoxia-related IHC Biomarkers and Regional FMISO Uptake in Tumor | p53 | 7 units on a scale 0=low, 8=high |
| 2 Year Overall Survival | Relationship Between Hypoxia-related IHC Biomarkers and Regional FMISO Uptake in Tumor | EGFR | 7 units on a scale 0=low, 8=high |
Comparison: The correlation between IHC values and FMISO uptake were analyzed using Spearman correlation where p values less than 0.05 were considered significant.p-value: <0.05Spearman Correlation
Secondary
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.
Time frame: Up to 2 years
Population: 11 tissue samples with Ki67 values were compared to FMISO uptake.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 Year Overall Survival | Relationship Between Ki67 and Regional FMISO Uptake in Tumor | 74 percentage of staining | Standard Deviation 18 |
Secondary
Response to XRT Using RECIST
Response for the XRT is evaluated by the radiation oncologists as per standard clinical protocols
Time frame: time to disease progression or 2 years following first FMISO scan
Population: PET/CT acquisition was obtained using non-diagnostic low dose CT attenuation scans at the time of PET/CT imaging that limited our ability to accurately measure tumor dimensions and due to lack of complete data, we were not able to fulfill this aim.