Panitumumab-IRDye800 for Brain Cancer

Overseen By Sandra Torres

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stanford University

Must not be taking: Antiarrhythmics

Disqualifiers: Pregnancy, Heart disease, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-5 days

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a special dye called panitumumab-IRDye800, which helps doctors see brain tumors more clearly during surgery. The trial aims to determine the safest dosage and assess how effectively it identifies cancer cells in patients with malignant glioma, a type of brain cancer. Individuals diagnosed with glioblastoma or vestibular schwannoma who plan to have their tumors surgically removed might be suitable candidates for this trial. The dye could enable surgeons to remove tumors more accurately. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain heart rhythm medications (like quinidine, procainamide, dofetilide, amiodarone, or sotalol).

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that panitumumab-IRDye800 is safe and effective for imaging brain tumors. In a study with 11 patients, no harmful side effects occurred, indicating the treatment was well-tolerated. Additionally, the safety and effects of panitumumab-IRDye800 align with those of panitumumab, a compound already used in other medical treatments, providing reassurance about its safety for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Panitumumab-IRDye800 because it offers a new way to visualize brain tumors during surgery. Unlike standard treatments such as surgery, radiation, and chemotherapy, this drug uses a special dye that binds to cancer cells, making them glow under near-infrared light. This unique feature helps surgeons see and remove tumors more precisely, potentially improving outcomes and reducing damage to healthy brain tissue.

What evidence suggests that panitumumab-IRDye800 is effective for diagnosing brain cancer?

Research has shown that panitumumab-IRDye800 can illuminate cancer cells during surgery, aiding surgeons in seeing the tumor more clearly and potentially improving the removal of cancerous tissue. In this trial, participants will receive varying doses of panitumumab-IRDye800, with some receiving a 50mg dose and others a 100mg dose, to determine the optimal dose for enhancing tumor visibility. Early findings suggest that patients with glioblastoma, a type of brain cancer, may benefit from better tumor visibility, potentially leading to improved surgical outcomes and survival. Although this treatment remains under study, its ability to highlight tumor cells offers a promising tool for surgeons. ^{1 3 6 7 8}

Who Is on the Research Team?

Gordon Li, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals who are scheduled for brain tumor surgery and have a malignant glioma. They must be deemed eligible for resection by their surgeon, may have had previous treatments like chemotherapy or radiation, and need to have an adequate platelet count. People with recent heart issues, history of bad reactions to monoclonal antibodies, pregnant or breastfeeding women, certain abnormal lab values, lung conditions like interstitial pneumonitis or pulmonary fibrosis can't participate.

Inclusion Criteria

I've had chemotherapy, radiation, or a biopsy and am considered a candidate for surgery.

Platelet count ≥ 75,000/mm^3

My surgeon has approved me for surgery.

Exclusion Criteria

My tumor cannot be surgically removed due to its location or other factors.

I have had interstitial pneumonitis or pulmonary fibrosis.

I am taking medication for heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive panitumumab-IRDye800 at varying doses 1 to 5 days before surgery, followed by NIR imaging during surgery

1-5 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and tumor-to-background ratio assessments

30 days

Long-term Follow-up

Further analysis of tissue samples and outcomes related to tumor-to-background ratio over an extended period

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Panitumumab-IRDye800

Trial Overview

The study is testing the safety and optimal dose of Panitumumab-IRDye800 during surgery in patients with malignant glioma. This substance binds to tumor cells making them glow under a special camera so surgeons can see the cancer more clearly compared to normal brain tissue.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 4 Interventions

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.

Group II: Cohort 3 -100mg panitumumab-IRDye800 Experimental Treatment 4 Interventions

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

Group III: Cohort 2 -100mg panitumumab-IRDye800 Experimental Treatment 4 Interventions

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.

Group IV: Cohort 1 -50mg panitumumab-IRDye800 Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Eben Rosenthal

Lead Sponsor

Trials

9

Recruited

200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Tumor-associated B-cells in glioblastoma express high levels of checkpoint molecules that inhibit their immune functions, suggesting a barrier to effective immunotherapy in brain tumors.

Targeting the TGFβ pathway and blocking specific integrins can enhance B-cell activity and improve the efficacy of immune-checkpoint blockade treatments, potentially leading to better outcomes for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-cells Drive Response to PD-1 Blockade in Glioblastoma Upon Neutralization of TGFβ-mediated Immunosuppression. Hou, D., Castro, B., Dapash, M., et al.[2023]

In a study involving 16 nude mice with patient-derived glioblastoma (GBM), panitumumab-IRDye800CW demonstrated a 30% higher tumor-to-background ratio compared to the standard agent 5-ALA, indicating better visualization of tumor margins during surgery.

Panitumumab-IRDye800CW also showed improved specificity for identifying tumor core and margins, suggesting it could enhance surgical resection outcomes and potentially improve survival rates for patients with GBM compared to 5-ALA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Panitumumab-IRDye800CW and 5-Aminolevulinic Acid to Provide Optical Contrast in a Model of Glioblastoma Multiforme. Napier, TS., Udayakumar, N., Jani, AH., et al.[2021]

The study demonstrated that the fluorescently labeled antibodies cetuximab-IRDye800CW and panitumumab-IRDye800CW are safe for use in surgical imaging, with minimal toxicities observed in 27 patients with head and neck squamous cell carcinoma.

Both antibodies showed similar pharmacodynamic properties, and no significant safety concerns were raised, indicating potential for other therapeutic antibodies to be repurposed for imaging with limited preclinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Gao, RW., Teraphongphom, N., de Boer, E., et al.[2019]

Rindopepimut, an immunotherapy targeting the EGFRvIII mutation, is the first of its kind to enter Phase III clinical trials for treating recurrent glioblastoma, a highly aggressive brain tumor.

The ReACT Phase II trial evaluated the combination of rindopepimut and bevacizumab in patients with EGFRvIII-positive recurrent glioblastoma, highlighting the potential of this approach to activate the immune response against tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ReACT Phase II trial: a critical evaluation of the use of rindopepimut plus bevacizumab to treat EGFRvIII-positive recurrent glioblastoma. Gatson, NT., Weathers, SP., de Groot, JF.[2018]

In a study involving 260 patients with recurrent EGFR-amplified glioblastoma, the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M) did not improve health-related quality of life (HRQoL) or neurological deterioration-free survival (NDFS) compared to standard treatments like temozolomide or lomustine.

Patients receiving Depatux-M experienced significant visual disorders, which were clinically relevant and consistent with known side effects of the drug, highlighting a safety concern despite the lack of overall survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma. Clement, PMJ., Dirven, L., Eoli, M., et al.[2021]

In a study involving 24 patients with head and neck squamous cell carcinoma, a fixed dose of 50 mg of the fluorescently labeled antibody panitumumab-IRDye800CW was identified as the optimal dose for enhancing fluorescence during surgery.

The study found that reducing the time between infusion and surgery to within 2 days significantly increased the fluorescence intensity of the tumors, suggesting that timing is crucial for effective imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer. Nishio, N., van den Berg, NS., van Keulen, S., et al.[2021]

The anti-EGFR antibody panitumumab-IRDye800 was found to be safe and effective for imaging high-grade gliomas (HGGs) in 11 patients, with no adverse events reported at both low (50 mg) and high (100 mg) doses.

This imaging agent demonstrated high sensitivity (95%) and specificity (96%) for detecting tumor tissue, allowing for improved intraoperative visualization of tumors, which could enhance surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Zhou, Q., van den Berg, NS., Rosenthal, EL., et al.[2021]

A prototype glioma cancer vaccine using a mix of antigens from both patient and donor tumor tissues showed promise in stopping tumor growth in a rat model of malignant glioma.

The vaccine was particularly effective when combined with immunostimulants like Bacille Calmette Guerin (BCG) and interleukin-2, or the TLR 7/8 activator resiquimod, indicating that these combinations enhance the immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Therapeutic Efficacy of Glioma Vaccines Based on Allo- and Syngeneic Antigens and Distinct Immunological Costimulation Activators. Stathopoulos, A., Pretto, C., Devillers, L., et al.[2021]

In a phase 3 trial involving 745 patients with newly diagnosed glioblastoma, the addition of the vaccine rindopepimut to standard chemotherapy did not significantly improve overall survival compared to the control group, with median survival times of 20.1 months versus 20.0 months, respectively.

The study was terminated for futility after an interim analysis, indicating that rindopepimut alone may not be effective in enhancing survival outcomes, suggesting that combination therapies may be necessary for immunotherapy to be effective in treating glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Weller, M., Butowski, N., Tran, DD., et al.[2023]

Panitumumab-IRDye800 has been developed as an effective intraoperative optical imaging agent for detecting EGFR-expressing tumors, showing high specificity and sensitivity in various mouse models with different levels of EGFR expression.

The study demonstrated a strong correlation between the level of EGFR expression in tumors and the uptake of the panitumumab-IRDye800, indicating its potential for precise tumor visualization during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of panitumumab-IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers. Bhattacharyya, S., Patel, N., Wei, L., et al.[2020]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03510208

Study Details | NCT03510208 | Panitumumab-IRDye800 in ...

The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery.

2.

clinicaltrials.stanford.edu

clinicaltrials.stanford.edu/trials/p/NCT03510208.html

Panitumumab-IRDye800 in Diagnosing Participants With ...

The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery.

3.

cdek.pharmacy.purdue.edu

cdek.pharmacy.purdue.edu/trial/NCT03510208/

Trial | NCT03510208

The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery.

4.

withpower.com

withpower.com/trial/phase-2-neoplasms-4-2018-709c4

Panitumumab-IRDye800 for Brain Cancer

This trial studies how well Panitumumab-IRDye800 works in making cancer cells glow during surgery for patients with malignant glioma.

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32606015/

Comparison of Panitumumab-IRDye800CW and 5 ... - PubMed

Improved margin definition and surgical resection using panitumumab-IRDye800 has the potential to improve surgical outcomes and survival in patients with GBM ...

6.

researchgate.net

researchgate.net/publication/324644475_Safety_of_panitumumab-IRDye800CW_and_cetuximab-IRDye800CW_for_fluorescence-guided_surgical_navigation_in_head_and_neck_cancers

Safety of panitumumab-IRDye800CW and cetuximab- ...

PDF | Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging.

7.

semanticscholar.org

semanticscholar.org/paper/Safety-of-panitumumab-IRDye800CW-and-for-surgical-Gao-Teraphongphom/760c4141f578d46e5bc34a358a270470874b568f

[PDF] Safety of panitumumab-IRDye800CW and cetuximab ...

... panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. ... Tumor-Specific Fluorescence-Guided Surgery for Pancreatic Cancer Using ...

8.

scholar.usuhs.edu

scholar.usuhs.edu/en/publications/safety-of-panitumumab-irdye800cw-and-cetuximab-irdye800cw-for-flu

Safety of panitumumab-IRDye800CW and cetuximab- ...

Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other ...