Clinical trial NCT00794339: Phase II Trial of 64Cu-ATSM PET/CT in Cervical Cancer
Official title: Copper Cu 64-ATSM and PET/CT Scan in Predicting Disease Progression in Patients With Newly-Diagnosed Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer Who Are Undergoing Chemoradiotherapy Per NCCN Guidelines
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: cervical squamous cell carcinoma
stage IIB cervical cancer
stage III cervical cancer
stage IV cervical cancer
stage IVA cervical cancer
stage IB cervical cancer
stage IIA cervical cancer
Lead sponsor: American College of Radiology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: American College of Radiology Imaging Network
First posted: 2008-11-20
Enrollment: 73
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: RATIONALE: Diagnostic procedures, such as 64Cu-labeled diacetyl-bis\[N4-methylthiosemicarbazone\] (copper Cu 64-ATSM) PET/CT scans, may help doctors predict how patients will respond to treatment.

PURPOSE: This phase II trial is studying how well copper Cu 64-ATSM PET/CT scans work in predicting disease progression in patients undergoing standard of care treatment with cisplatin and radiation therapy (external beam and brachytherapy) per National Comprehensive Cancer Network (NCCN) guidelines for newly-diagnosed stage IB, stage II, stage III, or stage IVA cervical cancer via the Federation of Gynecology and Obstetrics (FIGO) staging systems.

Detailed description: OBJECTIVES:

Primary

* To define the role of pre-therapy \^64Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) (copper Cu 64-ATSM) in predicting prognosis and determining the behavior of an invasive squamous cell cervical cancer in patients with newly-diagnosed stage IB2-IVA cervical squamous cell carcinoma.
* To determine whether higher copper Cu 64-ATSM uptake is associated with lower progression-free survival of these patients after chemoradiotherapy.

Secondary

* To determine if higher copper Cu 64-ATSM uptake is associated with lower overall survival of these patients.
* To determine if higher copper Cu 64-ATSM uptake is associated with earlier primary cervical tumor recurrence and a higher rate of development of distant metastatic disease in these patients.
* To determine if higher copper Cu 64-ATSM uptake is associated with a lower frequency of complete metabolic response on 2-Deoxy-2-\[18F\]fluoroglucose (FDG) -PET/CT scan performed 3 months after completion of radiotherapy and chemotherapy.
* To estimate the accuracy of copper Cu 64-ATSM uptake as a predictor of progression-free survival, overall survival, primary tumor recurrence, and future development of distant metastatic disease in these patients.
* To evaluate the performance of copper Cu 64-ATSM uptake as a predictor of lymph node metastasis at study entry.
* To evaluate whether copper Cu 64-ATSM uptake correlates with tumor volume at study entry.
* To examine the relationship between tumor uptake of copper Cu 64-ATSM and other markers of tumor hypoxia, including Vascular endothelial growth factor (VEGF) , Glucose transporter 1 (GLUT1), Carbonic anhydrase IX (CA9/CA IX), and Osteopontin (OPN).
* To compare the predictive ability of pre-therapy copper Cu 64-ATSM-PET to that of post-therapy FDG-PET/CT scan.
* To assess whether pre-therapy FDG-PET/CT findings are predictive of progression-free survival.

OUTLINE: This is a multicenter study.

Patients receive copper Cu 64-ATSM IV and undergo PET/CT scan over 30 minutes 30-40 minutes later. Within 4 weeks after copper Cu 64-ATSM-PET/CT scan, patients begin planned concurrent standard of care chemoradiotherapy comprising 6 weeks of radiotherapy (external beam and brachytherapy)and weekly cisplatin administration per NCCN guidelines. Patients then undergo FDG-PET/CT scan 3 months after completion of chemoradiotherapy.

Tissue samples from previously collected cervical biopsy (obtained for diagnosis) are used for detecting hypoxic markers by immunohistochemistry analysis.

After completion of study intervention, patients are followed for every 3 months for 2 years and then every 6 months for 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed primary invasive cervical squamous cell carcinoma

  * Newly diagnosed disease
  * Stage IB2 - IVA disease based on FIGO staging system
* Plan to receive standard of care treatment with concurrent cisplatin and radiation therapy (external beam and brachytherapy) per NCCN guidelines

  * Must be scheduled to receive 6 weekly courses of cisplatin
* Meets 1 of the following criteria:

  * Pelvic nodal (or no nodal) disease only by FDG-PET/CT scan within 4 weeks of enrollment
  * Para-aortic nodal metastasis by FDG-PET/CT scan within 4 weeks of enrollment, and patient will undergo radiotherapy to para-aortic nodes
  * FDG-PET/CT scan at baseline if not meeting any of the above criteria
* No stage IVB disease (distant metastases or supraclavicular metastasis) confirmed by FDG-PET/CT scan
* No recurrent invasive carcinoma of the uterine cervix regardless of previous treatment
* No know metastases to lungs, supraclavicular lymph nodes, or other organs outside of the pelvis or abdominal lymph nodes at time of diagnosis

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able to lie flat for the duration of the PET/CT scan
* No septicemia or severe infection
* No uncontrolled or poorly controlled diabetes
* No circumstances that would prevent completion of imaging studies or required clinical follow-up
* No other prior or concurrent invasive malignancies, with the exception of non-melanoma skin cancer, within the past 5 years

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior pelvic or abdominal lymphadenectomy
* No prior pelvic radiation therapy
* No previous cancer treatment contraindicates this protocol therapy

Primary outcomes:
measure: Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy
timeFrame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Secondary outcomes:
measure: Copper Cu 64-ATSM T/M Uptake and Overall Survival
timeFrame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
measure: Relationship Between Copper Cu 64-ATSM Uptake and Complete Metabolic Response
timeFrame: 3 months after completion of chemoradiation
measure: Primary Tumor Recurrence
timeFrame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
measure: Lymph Node Metastasis at Baseline
timeFrame: Two weeks
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
timeFrame: baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia
timeFrame: baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia
timeFrame: Baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
timeFrame: baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Staining Intensity Score: as a Marker of Tumor Hypoxia
timeFrame: baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia
timeFrame: Baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
timeFrame: baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia
timeFrame: baseline
measure: Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia
timeFrame: Baseline
measure: Relationship Between Copper Cu 64-ATSM Uptake and Development of Distant Metastasis
timeFrame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
Study officials:
affiliation: Mallinckrodt Institute of Radiology at Washington University Medical Center
name: Farrokh Dehdashti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: David A. Mankoff, MD, PhD
role: STUDY_CHAIR
References: