FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: 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
• Intervention / Treatment: Other: 18F-fluoromisonidazole; Radiation: fluorodeoxyglucose F 18; Procedure: positron emission tomography; Other: tissue oxygen measurement

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic FMISO AND FDG PET; 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; Undergo ^18F FMISO PET scan; Other Names: 18F-FMISO; Radiation: fluorodeoxyglucose F 18; Undergo ^18F FDG PET scan; Other Names: 18FDG; FDG; Procedure: positron emission tomography; Undergo ^18F-FMISO and ^18F FDG PET scan; Other Names: PET; FDG-PET; PET scan; tomography, emission computed; Other: tissue oxygen measurement; Undergo ^18 F FMISO PET and ^18F FDG PET

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joseph Rajendran, University of Washington

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Estimate): December 30, 2016
• Last Update Submitted That Met QC Criteria: December 28, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Signs and Symptoms, Respiratory; Uterine Cervical Neoplasms; Hypoxia; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: NCI-2009-00257 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); UW IRB# 6143 (Other Identifier: University of Washington Medical Center); 7958 (CTEP); N01CM37008 (Other Identifier: US NIH Grant/Contract Award Number:)