Clinical Trials /

Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery

NCT03510208

Description:

The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery. Panitumumab-IRDye800 can attach to tumor cells and make them more visible using a special camera during surgery, which may help surgeons better distinguish tumor cells from normal brain tissue and identify small tumors that cannot be seen using current imaging methods.

Related Conditions:
  • Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery
  • Official Title: Phase I/II, Open-Label Study Evaluating the Efficacy and Pharmacokinetics of Panitumumab-IRDye800 as an Optical Imaging Agent to Detect Neoplasms During Neurosurgical Procedures

Clinical Trial IDs

  • ORG STUDY ID: IRB-43179
  • SECONDARY ID: NCI-2018-00536
  • SECONDARY ID: BRNCNS0009
  • SECONDARY ID: 43179
  • NCT ID: NCT03510208

Conditions

  • Malignant Brain Neoplasm
  • Malignant Glioma

Interventions

DrugSynonymsArms
PanitumumabABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, VectibixCohort 1 -50mg panitumumab-IRDye800
Panitumumab-IRDye800Panitumumab IRDye 800, RDye800-Panitumumab ConjugateCohort 1 -50mg panitumumab-IRDye800

Purpose

The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery. Panitumumab-IRDye800 can attach to tumor cells and make them more visible using a special camera during surgery, which may help surgeons better distinguish tumor cells from normal brain tissue and identify small tumors that cannot be seen using current imaging methods.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine/verify the safety and pharmacokinetic profile of panitumumab conjugated to the
      optical dye IRDye800CW (panitumumab-IRDye800), as an imaging agent in patients undergoing
      surgery for malignant glioma.

      SECONDARY OBJECTIVES:

      I. Determine the efficacy of panitumumab IRDye800 in identifying malignant glioma compared to
      surrounding normal central nervous system tissue.

      II. Determine whether a loading dose of panitumumab is necessary to achieve an effective
      tumor-to-background ratio.

      III. Determine the optimal timing of the surgical procedure to maximize the
      tumor-to-background ratio.

      OUTLINE: This is a phase I, dose escalation study of panitumumab-IRDye800 followed by a phase
      II study.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 -50mg panitumumab-IRDye800ExperimentalA panitumumab-IRDye800 dose of 50mg (Cohort 1) with or without a 100 mg loading dose of unlabeled panitumumab will be injected 1 to 5 days before the planed standard of care surgery. Participants then undergo NIR imaging during standard of care surgery 1-5 days after receiving panitumumab-IRDye800.
  • Panitumumab
  • Panitumumab-IRDye800
Cohort 2 -100mg panitumumab-IRDye800ExperimentalA panitumumab-IRDye800 dose of 100mg (Cohort 2) with or without a 100 mg loading dose of unlabeled panitumumab will be injected 1 to 5 days before the planed standard of care surgery. Participants then undergo NIR imaging during standard of care surgery 1-5 days after receiving panitumumab-IRDye800.
  • Panitumumab
  • Panitumumab-IRDye800
Cohort 3 -100mg panitumumab-IRDye800ExperimentalCohort 3 dose will be determined based on Cohort 1 and Cohort 2, with or without a 100 mg loading dose of unlabeled panitumumab will be injected 1 to 5 days before the planed standard of care surgery
  • Panitumumab
  • Panitumumab-IRDye800

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects with suspected brain tumors undergoing surgical removal as their standard of
             care will be eligible; these may include subjects' status post chemotherapy and/or
             radiation or subjects who have undergone diagnostic biopsy for their original
             diagnosis and are assessed to be candidates for resection

          -  Subjects must be eligible for resection as determined by the operating surgeon

          -  Platelet count ≥ 75,000/mm^3

        Exclusion Criteria:

          -  Received an investigational drug within 30 days prior to first dose of
             panitumumab-IRDye800

          -  Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive
             heart failure (CHF); significant liver disease; or unstable angina within 6 months
             prior to enrollment

          -  History of infusion reactions to monoclonal antibody therapies

          -  Pregnant or breastfeeding

          -  Evidence of corrected QT (QTc) prolongation on pre-treatment electrocardiography (ECG)
             (greater than 440ms in males or greater than 460ms in females)

          -  Thyroid-stimulating hormone (TSH) ≥ 13 micro international units/mL

          -  Magnesium, potassium and calcium < the lower limit of normal per institution normal
             lab values

          -  Other lab values that in the opinion of the primary surgeon would prevent surgical
             resection

          -  Subjects receiving class IA (quinidine, procainamide) or class III (dofetilide,
             amiodarone, sotalol) antiarrhythmic agents

          -  Subjects with a history or evidence of interstitial pneumonitis or pulmonary fibrosis

          -  Subjects not deemed to be appropriate candidates for optimal resection of tumor based
             on location, involvement of eloquent brain, satellite lesions, or other factors not
             specifically listed here
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of grade 2 or higher adverse events which have been determined to be clinically significant and definitely, probably, or possibly related to the study treatment, graded according to Common Terminology Criteria for Adverse Effects (CTCAE) v. 4.0
Time Frame:Up to 30 days
Safety Issue:
Description:Descriptive statistical analysis of subject disposition, baseline characteristics, exposure to study drug, and adverse events will be performed. Descriptive statistics for continuous data will include mean, standard deviation, median, minimum, maximum, and inter-quartile values. Frequencies and percentages will be used to summarize categorical data.

Secondary Outcome Measures

Measure:Tumor to background ratio (TBR)
Time Frame:30 days from study treatment
Safety Issue:
Description:TBR is defined as the fluorescence intensity of tumor tissue compared to that or normal surrounding tissue as determined by ex vivo pathological imaging. Will be analyzed with the individual specimen as the unit of analysis using the Wilcoxon signed rank test.
Measure:Panitumumab Loading Dose
Time Frame:30 days
Safety Issue:
Description:The fluorescence intensity of tissue obtained from patients undergoing surgery will be evaluated as an indicator of whether or not the loading dose of panitumumab is necessary to achieve an effective tumor-to-background ratio (TBR). The Fluorescence intensity of tissue will be assessed on the specimens collected on the day of surgery (Day 1-5 Post infusion), in group a vs group b, for Cohorts 1 and 2, in order to determine the tumor-to-background ratio (TBR). The outcome will be expressed as TBR by group and cohort. TBR will be reported as means +/- STD.
Measure:Optimal Timing of Surgical Procedure
Time Frame:1 year
Safety Issue:
Description:The fluorescence intensity of tissue collected at surgery will be measured 1 to 5 days after infusion, and the outcome will be assessed as highest daily mean tumor-to-background ratio (TBR), with standard deviation. The tissue analysis to obtain the outcome data will occur within 1 year from surgery.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eben Rosenthal

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