Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery

Phase 1

Recruiting

• Conditions: Malignant Brain Neoplasm; Malignant Glioma
• Interventions: Procedure: Near-Infrared Fluorescence Imaging; Biological: Panitumumab; Drug: Panitumumab-IRDye800; Device: POINPOINT-IR9000

• Registration Number: NCT03510208
• Lead Sponsor: Eben Rosenthal

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.

Study Timeline

• Study First Submitted: 2018-04-12
• Study First Submitted QC: 2018-04-17
• Study First Posted: 2018-04-27
• Study Start: 2018-05-16
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

1. One of the following:

1. Cohorts 1, 2, and 3: Participants with suspected or confirmed diagnosis of glioblastoma

2. Cohort 4: Participants with suspected or confirmed diagnosis of vestibular schwannoma

   2.) Planned surgical removal of the tumor as part of standard of care. This may include participants postchemotherapy, post-radiation, and/or participants who have undergone diagnostic biopsy for their original diagnosis and are felt to be candidates for resection.

   3. Participant age ≥ 18 years.

   4. Participants or their designated advocates must be willing to and capable of providing informed consent and willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

Exclusion Criteria

1. Received an investigational drug within 30 days prior to first dose of Panitumumab-IRDye800.

2. Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease as determined by PI; or unstable angina within 6 months prior to enrollment.

3. History of infusion reactions to monoclonal antibody therapies

4. Pregnant or breastfeeding.

5. Evidence of QTc prolongation on pretreatment ECG (greater than 440 ms in males or greater than 460 ms in females).

6. Any of the following lab values:

   1. Platelet count < 75,000/mm3
   2. TSH ≥ 13 micro International Units/mL.
   3. Magnesium, potassium, or calcium < each respective upper limit of normal
   4. Serum creatinine > 1.5 times upper limit of normal

7. Participants receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.

8. Participants with a history or evidence of interstitial pneumonitis or pulmonary fibrosis.

9. Participants not deemed by PI 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 -50mg panitumumab-IRDye800	Near-Infrared Fluorescence Imaging	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.
Cohort 1 -50mg panitumumab-IRDye800	Panitumumab	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.
Cohort 1 -50mg panitumumab-IRDye800	POINPOINT-IR9000	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.
Cohort 2 -100mg panitumumab-IRDye800	Near-Infrared Fluorescence Imaging	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 2 -100mg panitumumab-IRDye800	Panitumumab	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 2 -100mg panitumumab-IRDye800	POINPOINT-IR9000	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 -100mg panitumumab-IRDye800	Near-Infrared Fluorescence Imaging	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
Cohort 3 -100mg panitumumab-IRDye800	Panitumumab	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
Cohort 3 -100mg panitumumab-IRDye800	POINPOINT-IR9000	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
Cohort 4	Near-Infrared Fluorescence Imaging	Cohort 4 will enroll 24 participants with vestibular schwannomas at the optimal dose of 100mg, as determined by the research team based on data analysis from the first two cohorts.
Cohort 4	Panitumumab	Cohort 4 will enroll 24 participants with vestibular schwannomas at the optimal dose of 100mg, as determined by the research team based on data analysis from the first two cohorts.
Cohort 4	POINPOINT-IR9000	Cohort 4 will enroll 24 participants with vestibular schwannomas at the optimal dose of 100mg, as determined by the research team based on data analysis from the first two cohorts.
Cohort 1 -50mg panitumumab-IRDye800	Panitumumab-IRDye800	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.
Cohort 3 -100mg panitumumab-IRDye800	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
Cohort 2 -100mg panitumumab-IRDye800	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 4	Panitumumab-IRDye800	Cohort 4 will enroll 24 participants with vestibular schwannomas at the optimal dose of 100mg, as determined by the research team based on data analysis from the first two cohorts.

Primary Outcome Measures

Name	Time	Method
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	Up to 30 days	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

Name	Time	Method
Tumor to background ratio (TBR)	30 days from study treatment	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	30 days	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	1 year	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.

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Palo Alto, California, United States