Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

• Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): City of Hope Medical Center

Tracking Information

• First Submitted Date: October 9, 2014
• First Posted Date: November 19, 2014
• Last Update Posted Date: April 10, 2019
• Study Start Date: June 8, 2015
• Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2014)

• Efficacy of each modality in locating cancer in each of four regions (primary, hepatic, extra-hepatic abdominal, and extra-abdominal) using lesion analysis [ Time Frame: Up to day 2 ]
  For lesion analysis, the efficacy of each modality will be evaluated where a successful outcome will be defined as the ability of at least one known tumor identified by conventional imaging modalities to be imaged using the M5A antibody. Using the standard statistical formulas, the number of true positives, false positives, true negatives, and false negatives, as well as the sensitivity and corresponding 95% confidence interval will be estimated using the method of Lee and Dubin or Rao and Scott, which accounts for the correlation between lesions within in same subject.
• Efficacy of each modality in locating cancer in each of four regions (primary, hepatic, extra-hepatic abdominal, and extra-abdominal) using region analysis [ Time Frame: Up to day 2 ]
  For region analysis, a successful outcome will be defined as the identification of suspicious tissue within a region. Using the standard statistical formulas, the number of true positives, false positives, true negatives, and false negatives, as well as the sensitivity and corresponding 95% confidence interval will be estimated using the method of Lee and Dubin or Rao and Scott, which accounts for the correlation between lesions within in same subject.
• Pharmacokinetic parameters of copper Cu 64 anti-CEA monoclonal antibody M5A [ Time Frame: Pre-dose, 30 minutes, and 1, 2, and 3-4 hours post start of infusion ]
  Blood samples will be drawn at various time points to construct the blood activity curve. Urine data will also be included in our analyses to check the whole body clearance curves. A computer pharmacokinetic model containing 5 compartments including blood, liver, residual body, urine and feces will be used to analyze time activity data. Residence times for various organs will be calculated from this pharmacokinetic model and/or uptake data. Different residence times for different isotopes, e.g. 64Cu, will be calculated by adjusting for physical decay. These times are then substituted into the OLINDA program.
• Immunogenicity properties of copper Cu 64 anti-CEA monoclonal antibody M5A [ Time Frame: Up to 3 months ]
  The patient's serum samples are evaluated in both a bridging radioimmunoassay and an HPLC assay. The sera are incubated with the appropriate radiolabeled M5A and then analyzed by HPLC size exclusion chromatography on a Superose 6 HR column.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02293954 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 14, 2014)

Incidence of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 3 months ]

Safety data will be displayed and abnormal laboratory values flagged. The frequency of adverse events will be tabulated by body system.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer
• Official Title: Pilot Study: Detection of Carcinomas Using 64Cu-Labeled M5A Antibody to Carcinoembryonic Antigen (CEA)
• Brief Summary: This pilot clinical trial studies copper Cu 64 anti-carcinoembryonic antigen (CEA) monoclonal antibody M5A positron emission tomography (PET) in diagnosing patients with CEA positive cancer. Diagnostic procedures, such as copper Cu 64 anti-CEA monoclonal antibody M5A PET, may help find and diagnose CEA positive cancer that may not be detected by standard diagnostic methods.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the ability of 64Cu labeled M5A antibody (copper Cu 64 anti-CEA monoclonal antibody M5A) to localize CEA positive cancers (such as gastrointestinal, lung, medullary thyroid and breast cancers), as determined by PET imaging.

SECONDARY OBJECTIVES:

I. To characterize the frequency of titer of the human anti-human antibody (HAHA) response to 64Cu labeled M5A antibody.

II. To determine the safety of administration of 64Cu labeled M5A antibody.

OUTLINE:

Patients receive copper Cu 64 anti-CEA monoclonal antibody M5A intravenously (IV) on day 0 and then undergo PET on day 1 and day 2.

After completion of study, patients are followed up at 1 and 3 months.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Breast Cancer
• Colon Cancer
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gastrointestinal Cancer
• Liver and Intrahepatic Biliary Tract Cancer
• Lung Cancer
• Metastatic Cancer
• Pancreatic Cancer
• Rectal Cancer
• Thyroid Gland Medullary Carcinoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

• Procedure: radionuclide imaging
  Given copper Cu 64 anti-CEA monoclonal antibody M5A IV
  Other Name: radionuclide scanning
• Procedure: positron emission tomography
  Undergo PET
  Other Names:

  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
• Other: laboratory biomarker analysis
  Correlative studies
• Other: pharmacological study
  Correlative studies
  Other Name: pharmacological studies
• Drug: Cu 64 anti-CEA monoclonal antibody M5A IV
  Cu 64 anti-CEA monoclonal antibody M5A IV

Study Arms

Experimental: Diagnostic (copper Cu 64 anti-CEA monoclonal antibody M5A PET)

Patients receive copper Cu 64 anti-CEA monoclonal antibody M5A IV on day 0 and then undergo PET on day 1 and day 2.

Interventions:

• Procedure: radionuclide imaging
• Procedure: positron emission tomography
• Other: laboratory biomarker analysis
• Other: pharmacological study
• Drug: Cu 64 anti-CEA monoclonal antibody M5A IV

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 12, 2016): 20
• Original Estimated Enrollment (submitted: November 14, 2014): 10
• Estimated Study Completion Date: June 2019
• Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have histologically confirmed primary or metastatic cancer; if biopsies were performed at an outside facility, the histology must be reviewed and confirmed by the Department of Pathology at the City of Hope
• Patients must have tumors that produce CEA as documented by a current or past history of an elevated serum CEA above the institutional limit of normal, or by immunohistochemical methods; NOTE: Patients with colorectal cancer are exempt from this requirement since > 95% are CEA positive
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Patients must have a known site of disease; please note, for patients undergoing neoadjuvant therapy, this requirement must be met retrospectively prior to the start of neoadjuvant therapy; patients who are in radiological/clinical remission after neoadjuvant therapy, prior to infusion of radiolabeled antibody, are still eligible
• Although not mandated by the protocol, the results of the CT scan and labs (complete blood count [CBC], comprehensive metabolic panel [CMP]) that are performed as part of the standard work up should be available and should have been done within 2 months prior to study entry
• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Prior therapy (chemotherapy, immunotherapy, radiotherapy) must be completed at least 2 weeks prior to infusion of radiolabeled antibody

Exclusion Criteria:

• Patients should not have any uncontrolled illness including ongoing or active infection
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to copper Cu 64 anti-CEA monoclonal antibody M5A (64Cu-M5A)
• Patients must not have received prior chemotherapy or radiation for >= 2 weeks before study enrollment
• Pregnant women are excluded from this study; breastfeeding should be discontinued is the mother is treated with 54Cu-m5A
• Any patient who has had exposure to mouse or chimeric (human/mouse) immunoglobulin and has antibody to the M5A
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02293954
• Other Study ID Numbers: 14238; NCI-2014-02079 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 14238 ( Other Identifier: City of Hope Medical Center )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: City of Hope Medical Center
• Study Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jeffrey Wong; City of Hope Medical Center

• PRS Account: City of Hope Medical Center
• Verification Date: April 2019