Clinical trial NCT00416455: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2006-12-28
Enrollment: 384
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Abdomen
timeFrame: Before surgery (FDG-PET-CT) and after surgery (pathology)
measure: The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Abdomen
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
Secondary outcomes:
measure: The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Pelvis
timeFrame: Before surgery (DCT) and after surgery (pathology)
measure: The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Pelvis
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: The Diagnostic Sensitivity of PET/CT for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: The Diagnostic Specificity of PET/CT for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Sensitivity for Detection of Lymph Node Metastasis in Abdomen by CT Alone
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Sensitivity for Detection of Lymph Node Metastasis in Pelvis by CT Alone
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Sensitivity Between for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis by CT Alone
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Specificity for Detection of Lymph Node Metastasis in Abdomen by CT Alone
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Specificity Between for Detection of Lymph Node Metastasis in Pelvis by CT Alone
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Specificity for Detection of Lymph Node Metastasis in Combination of Abdomen and Pelvis by CT Alone
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Percentage of Participants in Whom PET/CT Detects Biopsy-proven Disease Outside the Abdominal Lymph Nodes
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Percentage of Participants in Whom PET/CT Detects Biopsy-proven Disease Outside the Pelvic Lymph Node
timeFrame: Before surgery (FDG-PET/CT) and after surgery (pathology)
measure: Cervical Cancer Patients With Adverse Events (Grade 3 or Higher) at Least Possibly Attributed to Extra-peritoneal or Laparoscopic Abdominal and Pelvic Lymphadenectomy
timeFrame: During surgery and up to 30 days after surgery.
measure: Cause of Delay in the Initiation of Chemo-radiation Therapy More Than 4 Weeks After PET/CT for Cervical Cancer Patients
timeFrame: Within 4 weeks from PET/CT
measure: Cause of Interruption in Radiation Therapy in Cervical Cancer Patients
timeFrame: Within 6 weeks after surgery
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles Health System
state: California
city: Sylmar
country: United States
facility: Olive View-University of California Los Angeles Medical Center
state: California
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University Medical Center
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Newark
country: United States
facility: UMDNJ - New Jersey Medical School
state: New Jersey
city: Brightwaters
country: United States
facility: Island Gynecologic Oncology
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Center -The Plaza
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Quebec City
country: Canada
facility: CHUQ - Pavilion Hotel-Dieu de Quebec
state: Quebec
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kagoshima City, Kagoshima
country: Japan
facility: Kagoshima City Hospital
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Jung-Ku
country: Korea, Republic of
facility: Keimyung University-Dongsan Medical Center
state: Daegu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
Study officials:
affiliation: NRG Oncology
name: Mostafa Atri
role: PRINCIPAL_INVESTIGATOR
References: