Phase II Trial of 64Cu-ATSM PET/CT in Cervical Cancer (ACRIN6682)

August 9, 2023 updated by: American College of Radiology

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

73

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Copper ATSM
pre-therapy pelvic 64Cu-ATSM-PET/CT with Pre- and post- therapy FDG PET/CT
Drug: 64Cu-ATSM
Other Names:
  • copper 64
  • 64Cu Diacetyl-bis(N4-methylthiosemicarbazone)
Drug: FDG
Other Names:
  • fludeoxyglucose F 18
  • Fluorodeoxyglucose (18F)
  • 18F-FDG
  • 18F-fluorodeoxyglucose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy
Time Frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years

Progression-free survival (PFS) evaluated every 3 months for first 2 years and every 6 months during year 3 to determine PFS at 3years.

Cu64-ATSM Uptake measured within 14 days of baseline Uptake is a measure of activity within a tumor

  1. the maximum standardized uptake value (SUVmax = tracer uptake in ROI / (injected activity / patient weight))
  2. Tumor-to-Muscle uptake ratio (T/M, An FDG-PET/CT-guided circular region of interest of 1.0-1.5 cm in diameter is drawn around the most intense region of the primary tumor to calculate the maximum uptake within the region. In addition, regions of interest are drawn on bilateral gluteal muscle groups on at least 3 slices, and the mean uptake is calculated. The T/M is the ratio of these measurements.)
every 3 months for first 2 years and every 6 months during year 3, up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Copper Cu 64-ATSM T/M Uptake and Overall Survival
Time Frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years

To determine if higher 64Cu-ATSM uptake on PET/CT is associated with lower Overall survival (OS) T/M Uptake measured within 14 days of baseline;

Overall survival (OS) is measured every 3 months for first 2 years and every 6 months during year 3,until time of death or 3 years from baseline.
every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Relationship Between Copper Cu 64-ATSM Uptake and Complete Metabolic Response
Time Frame: 3 months after completion of chemoradiation
Complete metabolic response determined by FDG PET/CT performed 3 months after completion of chemoradiation By definition, metabolic response (as defined by NCI Concept ID: C3897320. https://www.ncbi.nlm.nih.gov/medgen/856914) is "the disappearance of metabolic tumor activity in target and non-target lesions, marked by a decrease in tumor standardized uptake value to the level of surrounding normal tissue (tumor uptake/normal uptake = ~1)"
3 months after completion of chemoradiation
Primary Tumor Recurrence
Time Frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
To determine if higher 64Cu ATSM uptake is associated with earlier primary cervical tumor recurrence images were taken every 3 months for first 2 years and every 6 months during year 3, up to 3 years and evaluated for primary cervical tumor recurrence
every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Lymph Node Metastasis at Baseline
Time Frame: Two weeks

Lymph nodes were evaluated at 5 locations: Pelvic, Common Iliac, Para Aortic, Mediastinal, and Supraclavicular

This outcome looks at the Association of Ratio of Tissue to Muscle (T/M) uptake with Lymph Node Metastases at Baseline
Two weeks
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
Time Frame: baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Carbonic anhydrase IX (CA-IX) markers using the

Percentage of Tumor Cells Staining Score:

0=<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=>66% tumor cells.
baseline
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia
Time Frame: baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with CA-IX markers using the

Staining Intensity Score:

0=No staining; 1=Weak staining; and 2=Moderate to strong staining.
baseline
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia
Time Frame: Baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with CA-IX markers using the

Composite Score (range 0-6):

Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2).
Baseline
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
Time Frame: baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with VEGF markers using the

Percentage of Tumor Cells Staining Score:

0=<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=>66% tumor cells.
baseline
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
Time Frame: baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Vascular endothelial growth factor (VEGF) markers using the

Staining Intensity Score:

0=No staining; 1=Weak staining; and 2=Moderate to strong staining.
baseline
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia
Time Frame: Baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Vascular endothelial growth factor (VEGF) markers using the

Composite Score (range 0-6):

Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2).
Baseline
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
Time Frame: baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Glucose transporter 1 (GLUT1) markers using the

Percentage of Tumor Cells Staining Score:

0=<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=>66% tumor cells.
baseline
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia
Time Frame: baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with GLUT-1 markers using the

Staining Intensity Score:

0=No staining; 1=Weak staining; and 2=Moderate to strong staining.
baseline
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia
Time Frame: Baseline

The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Glucose transporter 1 (GLUT1) markers using the

Composite Score (range 0-6):

Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2).
Baseline
Relationship Between Copper Cu 64-ATSM Uptake and Development of Distant Metastasis
Time Frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Existence of distant metastasis was evaluated every 3 months for first 2 years and every 6 months during year 3 Copper Cu 64-ATSM Uptake (T/M) measured within 14 days of baseline;
every 3 months for first 2 years and every 6 months during year 3, up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

American College of Radiology

Collaborators

National Cancer Institute (NCI)
American College of Radiology Imaging Network

Investigators

  • Principal Investigator: Farrokh Dehdashti, MD, Mallinckrodt Institute of Radiology at Washington University Medical Center
  • Study Chair: David A. Mankoff, MD, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 29, 2009

Primary Completion (Actual)

December 31, 2011

Study Completion (Actual)

December 31, 2011

Study Registration Dates

First Submitted

November 19, 2008

First Submitted That Met QC Criteria

November 19, 2008

First Posted (Estimated)

November 20, 2008

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 9, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000624407
  • ACRIN-6682 (Other Grant/Funding Number: ACRIN Foundation)
  • U01CA080098 (U.S. NIH Grant/Contract)
  • U01CA079778 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

See NCI data Sharing Policy

IPD Sharing Time Frame

July 2009

IPD Sharing Access Criteria

Public

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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