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

Phase 1

Completed

Conditions: Endometrial Clear Cell Carcinoma
Stage IIA Cervical Cancer
Stage IVA Cervical Cancer
Cervical Squamous Cell Carcinoma
Stage II Endometrial Carcinoma
Cervical Small Cell Carcinoma
Stage I Endometrial Carcinoma
Stage IB Cervical Cancer
Stage IIB Cervical Cancer
Stage III Cervical Cancer

Interventions: 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

Registration Number: NCT00416455

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 384

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	positron emission tomography	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.
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	diagnostic lymphadenectomy	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.
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	magnetic resonance imaging	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.
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	fludeoxyglucose F 18	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.
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	lymph node biopsy	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.
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	computed tomography	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.
Treatment (diagnostic scans, surgery, chemotherapy, radiation)	ferumoxtran-10	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.

Primary Outcome Measures

Name	Time	Method
The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Abdomen	Before surgery (FDG-PET-CT) and after surgery (pathology)	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.
The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Abdomen	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.

Secondary Outcome Measures

Name	Time	Method
The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Sensitivity for Detection of Lymph Node Metastasis in Pelvis by CT Alone	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Specificity Between for Detection of Lymph Node Metastasis in Pelvis by CT Alone	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Cervical Cancer Patients With Adverse Events (Grade 3 or Higher) at Least Possibly Attributed to Extra-peritoneal or Laparoscopic Abdominal and Pelvic Lymphadenectomy	During surgery and up to 30 days after surgery.	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.
The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Pelvis	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Cause of Interruption in Radiation Therapy in Cervical Cancer Patients	Within 6 weeks after surgery	Number of cervical cancer patients with reasons of interruption in radiation therapy
The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Pelvis	Before surgery (DCT) and after surgery (pathology)	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.
Sensitivity Between for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis by CT Alone	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Cause of Delay in the Initiation of Chemo-radiation Therapy More Than 4 Weeks After PET/CT for Cervical Cancer Patients	Within 4 weeks from PET/CT	Number of cervical cancer patients with reasons of delay in the initiation of chemo-radiation therapy
Sensitivity for Detection of Lymph Node Metastasis in Abdomen by CT Alone	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Specificity for Detection of Lymph Node Metastasis in Abdomen by CT Alone	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
Specificity for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis by CT Alone	Before surgery (FDG-PET/CT) and after surgery (pathology)	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.
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)

Trial Locations

Locations (33): Jonsson Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
CHUQ - Pavilion Hotel-Dieu de Quebec
🇨🇦
Quebec City, Quebec, Canada
Montefiore Medical Center-Einstein Campus
🇺🇸
Bronx, New York, United States
Saitama Medical University International Medical Center
🇯🇵
Saitama, Japan
Gangnam Severance Hospital
🇰🇷
Seoul, Korea, Republic of
Olive View-University of California Los Angeles Medical Center
🇺🇸
Sylmar, California, United States
University of California at Los Angeles Health System
🇺🇸
Los Angeles, California, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Island Gynecologic Oncology
🇺🇸
Brightwaters, New York, United States
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Providence Cancer Center -The Plaza
🇺🇸
Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸
Portland, Oregon, United States
Georgia Regents University Medical Center
🇺🇸
Augusta, Georgia, United States
Sarasota Memorial Hospital
🇺🇸
Sarasota, Florida, United States
UMDNJ - New Jersey Medical School
🇺🇸
Newark, New Jersey, United States
Weill Medical College of Cornell University
🇺🇸
New York, New York, United States
Keimyung University-Dongsan Medical Center
🇰🇷
Jung-Ku, Daegu, Korea, Republic of
Kagoshima City Hospital
🇯🇵
Kagoshima City, Kagoshima, Japan
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States
Hokkaido University Hospital
🇯🇵
Sapporo, Hokkaido, Japan
Brooke Army Medical Center
🇺🇸
Fort Sam Houston, Texas, United States
Korea Cancer Center Hospital
🇰🇷
Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of