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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Small Cell Carcinoma, Cervical Squamous Cell Carcinoma, Endometrial Clear Cell Carcinoma, Endometrial Papillary Serous Carcinoma, Stage I Endometrial Carcinoma, Stage IB Cervical Cancer, Stage II Endometrial Carcinoma, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer, Stage III Endometrial Carcinoma, Stage IVA Cervical Cancer

Intervention / Treatment
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* Radiation: fludeoxyglucose F 18
* Procedure: positron emission tomography
* Procedure: computed tomography
* Drug: ferumoxtran-10
* Procedure: magnetic resonance imaging
* Procedure: diagnostic lymphadenectomy
* Procedure: lymph node biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (diagnostic scans, surgery, chemotherapy, radiation)<br>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. | Radiation: fludeoxyglucose F 18<br>* Undergo FDG PET/CT<br>* Other names: FDG;Procedure: positron emission tomography<br>* Undergo FDG PET/CT<br>* Other names: tomography, emission computed;Procedure: computed tomography<br>* Undergo FDG PET/CT<br>* Other names: tomography, computed;Drug: ferumoxtran-10<br>* Undergo femoxtran-10 MRI<br>* Other names: USPIO;Procedure: magnetic resonance imaging<br>* Undergo femoxtran-10 MRI<br>* Other names: nuclear magnetic resonance imaging;Procedure: diagnostic lymphadenectomy<br>* Undergo extraperitoneal, laparoscopic, or trans-peritoneal lymphadenectomy<br>Procedure: lymph node biopsy<br>* Undergo pelvic and abdominal lymph node biopsy<br>* Other names: Biopsy of Lymph Node;|

What is the study measuring?
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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 |