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Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery

Primary Purpose

Malignant Brain Neoplasm, Malignant Glioma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Near-Infrared Fluorescence Imaging
Panitumumab
Panitumumab-IRDye800
POINPOINT-IR9000
Sponsored by
Eben Rosenthal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Malignant Brain Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1 -50mg panitumumab-IRDye800

Cohort 2 -100mg panitumumab-IRDye800

Cohort 3 -100mg panitumumab-IRDye800

Arm Description

A 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.

A 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.

Cohort 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

Outcomes

Primary Outcome Measures

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
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

Tumor to background ratio (TBR)
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.
Panitumumab Loading Dose
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.
Optimal Timing of Surgical Procedure
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.

Full Information

First Posted
April 12, 2018
Last Updated
April 14, 2023
Sponsor
Eben Rosenthal
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT03510208
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 16, 2018 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eben Rosenthal
Collaborators
National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Brain Neoplasm, Malignant Glioma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 -50mg panitumumab-IRDye800
Arm Type
Experimental
Arm Description
A 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.
Arm Title
Cohort 2 -100mg panitumumab-IRDye800
Arm Type
Experimental
Arm Description
A 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.
Arm Title
Cohort 3 -100mg panitumumab-IRDye800
Arm Type
Experimental
Arm Description
Cohort 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
Intervention Type
Procedure
Intervention Name(s)
Near-Infrared Fluorescence Imaging
Other Intervention Name(s)
NIR Fluorescence Imaging, NIR Optical Imaging
Intervention Description
Undergo NIR imaging
Intervention Type
Biological
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Panitumumab-IRDye800
Other Intervention Name(s)
Panitumumab IRDye 800, RDye800-Panitumumab Conjugate
Intervention Description
Given IV
Intervention Type
Device
Intervention Name(s)
POINPOINT-IR9000
Intervention Description
Intraoperative camera capable of exciting and detecting near infrared (NIR) dyes. Imaging will be performed on subjects during surgery and/or on ex-vivo resected tissues in the surgery suite ("back table").
Primary Outcome Measure Information:
Title
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
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.
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
Tumor to background ratio (TBR)
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.
Time Frame
30 days from study treatment
Title
Panitumumab Loading Dose
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.
Time Frame
30 days
Title
Optimal Timing of Surgical Procedure
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon Li
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery

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