Fludeoxyglucose (FDG) F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

Utility of Preoperative FDG-PET/CT Scanning Prior to Primary Chemoradiation Therapy to Detect Retroperitoneal Lymph Node Metastasis in Patients With Locoregionally Advanced Carcinoma of the Cervix (IB2, IIA ≥ 4 CM, IIB-IVA) or Endometrium (Grade 3 Endometrioid Endometrial Carcinoma; Serous Papillary Carcinoma, Clear Cell Carcinoma, or Carcinosarcoma (Any Grade); and Grade 1 OR 2 Endometrioid Endometrial Carcinoma With Cervical Stromal Involvement Overt in Clinical Examination or Confirmed by Endocervical Curettage

This phase I/II trial is studying how well fludeoxyglucose F 18 PET scan, CT scan, and ferumoxtran-10 MRI scan finds lymph node metastasis before undergoing chemotherapy and radiation therapy in patients with locally advanced cervical cancer or high-risk endometrial cancer. Diagnostic procedures, such as a fludeoxyglucose F 18 positron emission tomography (PET) scan, computed tomography (CT) scan, and ferumoxtran-10 magnetic resonance imaging (MRI) scan, may help find lymph node metastasis in patients with cervical cancer or endometrial cancer.

Study Overview

• Status: Completed
• Conditions: Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Cervical Small Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Endometrial Clear Cell Carcinoma; Stage III Endometrial Carcinoma; Cervical Adenosquamous Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage II Endometrial Carcinoma; Stage I Endometrial Carcinoma
• Intervention / Treatment: Procedure: computed tomography; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography; Drug: ferumoxtran-10; Procedure: magnetic resonance imaging; Procedure: diagnostic lymphadenectomy; Procedure: lymph node biopsy

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the diagnostic sensitivity and specificity of preoperative fludeoxyglucose F 18 positron emission tomography (FDG-PET)/CT scanning and ferumoxtran-10 MRI scanning in identifying metastases to abdominal (common iliac, para-aortic, and paracaval) lymph nodes in patients with locoregionally advanced cervical carcinoma.

II. Determine the diagnostic sensitivity and specificity of preoperative FDG-PET/CT scanning and ferumoxtran-10 MRI scanning in identifying metastases to retroperitoneal abdominal lymph nodes in patients with high-risk endometrial cancer.

SECONDARY OBJECTIVES:

I. Determine the diagnostic sensitivity and specificity of preoperative FDG-PET/CT scanning and ferumoxtran-10 MRI scanning in identifying metastases to pelvic lymph nodes and pelvic and abdominal lymph nodes combined in patients with locoregionally advanced cervical carcinoma or high-risk endometrial cancer.

II. Compare the additive diagnostic value of CT fusion (PET/CT scan) vs PET scanning alone in identifying metastases to pelvic, abdominal, and combined (all regions) lymph nodes in these patients.

III. Compare the diagnostic sensitivity and specificity of PET/CT scanning vs ferumoxtran-10 MRI scanning in identifying metastases to pelvic, abdominal, and combined lymph nodes in these patients.

IV. Compare the diagnostic sensitivity and specificity of ferumoxtran-10 MRI vs MRI alone, in terms of size criteria in the abdomen and pelvis, in these patients.

V. Determine the percentage of patients with locoregionally advanced cervical cancer or high-risk endometrial cancer who have biopsy-proven disease outside the abdominal or pelvic lymph nodes detected by PET/CT scanning.

VI. Determine the accuracy of MRI in determining the depth of myometrial invasion and involvement of cervix in patients with high-risk endometrial cancer.

VII. Determine the complications associated with extraperitoneal or laparoscopic abdominal and pelvic lymphadenectomy in patients with locoregionally advanced cervical cancer.

VIII. Determine the cause(s) of delay in the initiation of radiotherapy or interruption in radiotherapy in patients with locoregionally advanced cervical cancer.

IX. Collect data on the adverse effects of ferumoxtran-10 in patients with locoregionally advanced cervical carcinoma or high-risk endometrial cancer.

X. Compare the size of lymph nodes in pre- and post-ferumoxtran-10 MRI's in a subset of forty patients.

OUTLINE: This is a multicenter study.

Patients receive fludeoxyglucose F 18 (FDG) IV followed 60 minutes later by positron emission tomography (PET)/CT scanning on day 1. Patients also receive ferumoxtran-10 IV over 30-45 minutes on day 1 (or 24-36 hours before MRI) and undergo MRI on day 2. Patients undergo extraperitoneal, laparoscopic, or trans-peritoneal lymphadenectomy with pelvic and abdominal lymph node biopsy within 2 weeks after PET/CT scan. Patients diagnosed with metastatic disease prior to lymph node biopsy proceed directly to primary treatment. Patients with cervical cancer undergo chemoradiotherapy within 4 weeks of PET/CT scan.

After completion of study therapy, patients are followed at 6 weeks, 6 months, every 3 months for 2 years, and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ - Pavilion Hotel-Dieu de Quebec
• Japan
  • Kagoshima City, Kagoshima, Japan, 892-8580
    • Kagoshima City Hospital
  • Saitama, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 135-720
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 139-706
    • Korea Cancer Center Hospital
  • Daegu
    • Jung-Ku, Daegu, Korea, Republic of, 700-712
      • Keimyung University-Dongsan Medical Center
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Health System
    • Sylmar, California, United States, 91342
      • Olive View-University of California Los Angeles Medical Center
  • Connecticut
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ - New Jersey Medical School
  • New York
    • Brightwaters, New York, United States, 11718
      • Island Gynecologic Oncology
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Einstein Campus
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center -The Plaza
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army 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 or cytologically confirmed diagnosis of 1 of the following:

  • Invasive carcinoma of the cervix meeting all of the following criteria:

    • Previously untreated, primary disease
    • Locoregionally advanced (stage IB2, IIA [>= 4 cm], or IIB-IVA) disease
    • Any cell type allowed

  • High-risk endometrial carcinoma meeting 1 of the following criteria:

    • Grade 3 endometrioid or non-endometrioid endometrial carcinoma (clear cell or serous papillary) or carcinosarcoma diagnosed from an endometrial biopsy or dilation and curettage or
    • Grade 1 or 2 endometrioid endometrial carcinoma with cervical stromal involvement overt on clinical examination or confirmed by endocervical curettage
• Under consideration for chemoradiotherapy (patients with cervical cancer)
• Undergone appropriate surgery for cervical or endometrial carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage

• Appropriate surgical candidate to undergo extraperitoneal or laparoscopic lymph node sampling OR hysterectomy and lymph node sampling

  • No surgery for patients with advanced lymphadenopathy
• No recurrent invasive carcinoma of the uterus or uterine cervix regardless of previous treatment
• No known metastases to the lungs or scalene lymph nodes

• No metastases to other organs outside of the pelvis or abdominal lymph nodes at the time of the original clinical diagnosis

  • Patients with endometrial cancer with known intraperitoneal disease are eligible provided they undergo pelvic and para-aortic lymphadenectomy per protocol
• Participants must be enrolled at an American College of Radiology Imaging Network (ACRIN)-affiliated institution that is accredited by Gynecologic Oncology Group (GOG)
• GOG performance status 0-2
• Creatinine within normal institutional limits OR, in participants with creatinine levels above institutional normal, glomerular filtration rate (GFR) must be > 60 mL/min; there is no lower limit of normal for serum creatinine for this protocol

• Ferritin levels =< 600 ng/mL OR saturation of transferrin level =< 50%

  • Patients with high levels of ferritin or transferrin are eligible if documented hematology rules out iron overload
• Not pregnant or nursing
• Negative pregnancy test
• No patients weighing greater than that allowable by the PET/CT scanner
• No renal abnormalities, such as a pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of the lymphadenectomy
• No history of anaphylactic or life-threatening allergic reactions to any contrast media
• No other invasive malignancies within the past 5 years with the exception of nonmelanoma skin cancer
• No contraindication to MRI (e.g., severe claustrophobia, pacemaker, aneurysm clips, defibrillators, or other institutional contraindication to MRI)
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to ferumoxtran-10 (e.g., iron preparations, parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations)
• No immunodeficiencies that would predispose patient to specific or nonspecific mediator release
• No history of cirrhosis
• No poorly controlled, insulin-dependent diabetes (i.e., fasting blood glucose level > 200 mg/dL)
• No prior pelvic or abdominal lymphadenectomy
• No prior pelvic radiotherapy
• No prior anticancer therapy that would contraindicate study participation
• No ferumoxides within the past 2 weeks
• No investigational agents within the past 30 days
• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Treatment (diagnostic scans, surgery, chemotherapy, radiation); Patients receive fludeoxyglucose F 18 (FDG) IV followed 60 minutes later by positron emission tomography (PET)/CT scanning on day 1. Patients also receive ferumoxtran-10 IV over 30-45 minutes on day 1 (or 24-36 hours before MRI) and undergo MRI on day 2. Patients undergo extraperitoneal, laparoscopic, or trans-peritoneal lymphadenectomy with pelvic and abdominal lymph node biopsy within 2 weeks after PET/CT scan. Patients diagnosed with metastatic disease prior to lymph node biopsy proceed directly to primary treatment. Patients with cervical cancer undergo chemoradiotherapy within 4 weeks of PET/CT scan.

Procedure: computed tomography; Undergo FDG PET/CT; Other Names: tomography, computed; Radiation: fludeoxyglucose F 18; Undergo FDG PET/CT; Other Names: 18FDG; FDG; Procedure: positron emission tomography; Undergo FDG PET/CT; Other Names: PET; FDG-PET; PET scan; tomography, emission computed; Drug: ferumoxtran-10; Undergo femoxtran-10 MRI; Other Names: Combidex; AMI-227; G-53425; Sinerem; USPIO; Procedure: magnetic resonance imaging; Undergo femoxtran-10 MRI; Other Names: MRI; NMRI; nuclear magnetic resonance imaging; NMR imaging; Procedure: diagnostic lymphadenectomy; Undergo extraperitoneal, laparoscopic, or trans-peritoneal lymphadenectomy; Procedure: lymph node biopsy; Undergo pelvic and abdominal lymph node biopsy; Other Names: Biopsy of Lymph Node

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Abdomen	The sensitivity is defined as the percentage of patients who test with lymph node metastases by pre-operative PET/CT among the patients who have lymph node metastases identified by post-surgery pathology in abdomen. The reported sensitivity is reader average sensitivity by seven experienced PET-CT readers.	Before surgery (FDG-PET-CT) and after surgery (pathology)
The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Abdomen	The specificity is defined as the percentage of patients who test without lymph node metastases by pre-operative PET/CT among the patients who do not have lymph node metastases identified by post-surgery pathology in abdomen. The reported specificity is reader average specificity by seven experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Pelvis	The sensitivity is defined as the percentage of patients who test with lymph node metastases by pre-operative PET/CT among the patients who have lymph node metastases identified by post-surgery pathology in pelvis. The reported sensitivity is reader-averaged sensitivity.	Before surgery (DCT) and after surgery (pathology)
The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Pelvis	The specificity is defined as the percentage of patients who test without lymph node metastases in pelvis by pre-operative PET/CT among the patients who do not have lymph node metastases in pelvis identified by post-surgery pathology. The reported specificity is reader-averaged specificity.	Before surgery (FDG-PET/CT) and after surgery (pathology)
The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis	The sensitivity is defined as the percentage of patients who test with lymph node metastases by pre-operative PET/CT among the patients who have lymph node metastases identified by post-surgery pathology in combination of abdomen and pelvis. The reported sensitivity is reader-average sensitivity.	Before surgery (FDG-PET/CT) and after surgery (pathology)
The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis	The specificity is defined as the percentage of patients who test without lymph node metastases by pre-operative PET/CT among the patients who do not have lymph node metastases identified by post-surgery pathology in combination of abdomen and pelvis. The reported specificity is reader-averaged specificity.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Sensitivity for Detection of Lymph Node Metastasis in Abdomen by CT Alone	The sensitivity is defined as the percentage of patients who test with lymph node metastases by pre-operative CT alone among the patients who have lymph node metastases identified by post-surgery pathology in abdomen. The reported estimate of sensitivity is reader-average sensitivity across all 7 experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Sensitivity for Detection of Lymph Node Metastasis in Pelvis by CT Alone	The sensitivity is defined as the percentage of patients who test with lymph node metastases by pre-operative either CT alone among the patients who have lymph node metastases identified by post-surgery pathology in pelvis. The reported estimate of sensitivity is reader-average sensitivity across all 7 experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Sensitivity Between for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis by CT Alone	The sensitivity is defined as the percentage of patients who test with lymph node metastases by pre-operative by CT alone among the patients who have lymph node metastases identified by post-surgery pathology in pelvis. The reported estimate of sensitivity is reader-average sensitivity across all 7 experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Specificity for Detection of Lymph Node Metastasis in Abdomen by CT Alone	The specificity is defined as the percentage of patients who test without lymph node metastases by pre-operative CT alone among the patients who do not have lymph node metastases identified by post-surgery pathology in pelvis. The reported estimate of specificity is reader-average specificity across all 7 experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Specificity Between for Detection of Lymph Node Metastasis in Pelvis by CT Alone	The specificity is defined as the percentage of patients who test without lymph node metastases by pre-operative byCT alone among the patients who do not have lymph node metastases identified by post-surgery pathology in pelvis. The reported estimate of specificity is reader-average specificity across all 7 experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Specificity for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis by CT Alone	The specificity is defined as the percentage of patients who test without lymph node metastases by pre-operative CT alone among the patients who do not have lymph node metastases identified by post-surgery pathology in pelvis. The reported estimate of specificity is reader-average specificity across all 7 experienced PET-CT readers.	Before surgery (FDG-PET/CT) and after surgery (pathology)
Percentage of Participants in Whom PET/CT Detects Biopsy-proven Disease Outside the Abdominal Lymph Nodes		Before surgery (FDG-PET/CT) and after surgery (pathology)
Percentage of Participants in Whom PET/CT Detects Biopsy-proven Disease Outside the Pelvic Lymph Node		Before surgery (FDG-PET/CT) and after surgery (pathology)
Cervical Cancer Patients With Adverse Events (Grade 3 or Higher) at Least Possibly Attributed to Extra-peritoneal or Laparoscopic Abdominal and Pelvic Lymphadenectomy	Number of participants with cervical cancer and a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v3.0.	During surgery and up to 30 days after surgery.
Cause of Delay in the Initiation of Chemo-radiation Therapy More Than 4 Weeks After PET/CT for Cervical Cancer Patients	Number of cervical cancer patients with reasons of delay in the initiation of chemo-radiation therapy	Within 4 weeks from PET/CT
Cause of Interruption in Radiation Therapy in Cervical Cancer Patients	Number of cervical cancer patients with reasons of interruption in radiation therapy	Within 6 weeks after surgery

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Mostafa Atri, NRG Oncology

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): July 16, 2016

Study Registration Dates

• First Submitted: December 27, 2006
• First Submitted That Met QC Criteria: December 27, 2006
• First Posted (ESTIMATE): December 28, 2006

Study Record Updates

• Last Update Posted (ACTUAL): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasms, Complex and Mixed; Neoplasm Metastasis; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Uterine Cervical Neoplasms; Carcinoma; Endometrial Neoplasms; Small Cell Lung Carcinoma; Lymphatic Metastasis; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Adenomyoepithelioma; Carcinoma, Adenosquamous; Carcinoma, Small Cell; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: NCI-2009-00600 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA027469 (U.S. NIH Grant/Contract); CDR0000521453; ACRIN 6671; GOG-0233/ACRIN 6671; GOG-0233-ACRIN 6671 (OTHER: NRG Oncology); GOG-0233 (OTHER: CTEP)