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

Cervical Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00416455
• Other study ID #: NCI-2009-00600
• Secondary ID: NCI-2009-00600CD
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2007
• Est. completion date: July 16, 2016

Study information

• Verified date: November 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 384
• Est. completion date: July 16, 2016
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Small Cell
• Carcinoma, Squamous Cell
• Cervical Adenocarcinoma
• Cervical Adenosquamous Cell Carcinoma
• Cervical Small Cell Carcinoma
• Cervical Squamous Cell Carcinoma
• Endometrial Clear Cell Carcinoma
• Endometrial Neoplasms
• Endometrial Papillary Serous Carcinoma
• Small Cell Lung 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
• Uterine Cervical Neoplasms

Intervention

Radiation:
• fludeoxyglucose F 18
Undergo FDG PET/CT

Procedure:
• positron emission tomography
Undergo FDG PET/CT
• computed tomography
Undergo FDG PET/CT

Drug:
• ferumoxtran-10
Undergo femoxtran-10 MRI

Procedure:
• magnetic resonance imaging
Undergo femoxtran-10 MRI
• diagnostic lymphadenectomy
Undergo extraperitoneal, laparoscopic, or trans-peritoneal lymphadenectomy
• lymph node biopsy
Undergo pelvic and abdominal lymph node biopsy

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	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
Secondary	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