Positron Emission Tomography Using Fluoromisonidazole F 18 and Fludeoxyglucose F 18 to Find Oxygen in Tumor Cells of Patients Undergoing Treatment for Newly Diagnosed Stage IB, Stage II, Stage III, or Stage IV Cervical Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00559377
First received: November 15, 2007
Last updated: June 10, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
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
Other: 18F-fluoromisonidazole
Radiation: fludeoxyglucose F 18
Procedure: positron emission tomography
Other: tissue oxygen measurement
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: For up to 2 years ] [ Designated as safety issue: No ]
    The first analysis will evaluate the value of pre-treatment FMISO results (T:B and HV) for all patients to predict the survival outcome variables. Multivariate Cox regression (Kalbfleisch 1980) will be used to analyze OS.

  • Disease-free survival (DFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Multivariate Cox regression (Kalbfleisch 1980) will be used to analyze DFS.

  • Response to radiotherapy as measured by standard Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Assessed up to 2 years ] [ Designated as safety issue: No ]
    Response analysis will be approached using multivariate logistic regression (McCullagh 1989). All patients included in the study must be assessed for response to treatment, even if there are major protocol treatment deviations or if they are ineligible.


Secondary Outcome Measures:
  • Relationship between hypoxia-related biomarkers (HIF1-α and VEGF by immunohistochemistry [IHC]), proliferation biomarkers (microvascular density, p53, and Ki-67 by IHC), and regional fluoromisonidazole F 18 uptake in tumor [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    We will perform ANOVA and Kruskal-Wallis analysis across the different categories to look for significant associations. The value of the biomarker analyses relates primarily to validating the information content of FMISO images.


Enrollment: 16
Study Start Date: November 2007
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diagnostic (^18F FMISO PET and ^18F 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. 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.
Other: 18F-fluoromisonidazole
Undergo ^18F FMISO PET scan
Other Name: 18F-FMISO
Radiation: fludeoxyglucose 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:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Other: tissue oxygen measurement
Undergo ^18 F FMISO PET and ^18F FDG PET

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559377

Locations
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Investigators
Principal Investigator: Joseph Rajendran University of Washington
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00559377     History of Changes
Other Study ID Numbers: NCI-2009-00257, NCI-2009-00257, CDR0000574114, UW-6143, UW IRB# 6143, 7958, N01CM37008
Study First Received: November 15, 2007
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Carcinoma
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Fluorodeoxyglucose F18
Fluoromisonidazole
Misonidazole
Anti-Infective Agents
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Diagnostic Uses of Chemicals
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Radiopharmaceuticals
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014