Panitumumab-IRDye800 Imaging for Pancreatic Cancer

Overseen By [e-mail] [e-mail]

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eben Rosenthal

Must not be taking: Antiarrhythmics

Disqualifiers: Recent MI, CHF, QT prolongation, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help surgeons visualize pancreatic cancer during surgery. It combines Panitumumab (Vectibix) with a dye that illuminates cancer cells, enabling more precise removal. The trial aims to determine the safest dose and assess its effectiveness. Individuals with pancreatic cancer scheduled for surgery may qualify for participation. As a Phase 1/Phase 2 trial, it seeks to understand the treatment's function in people and measure its effectiveness in an initial, smaller group, offering participants the opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients who are taking certain heart rhythm medications. It's best to discuss your specific medications with the trial team.

What prior data suggests that Panitumumab-IRDye800 is safe for imaging pancreatic cancer?

Research has shown that panitumumab-IRDye800 is generally safe for people. In earlier studies, this treatment proved safe and useful for helping surgeons by making tumors glow. This involves a special dye combined with panitumumab, a type of drug. The dye helps doctors see cancer more clearly during surgery.

While panitumumab-IRDye800 remains under study, panitumumab itself has been used in other treatments for a long time. The FDA first approved it in 2006 for different uses, which provides some confidence about its safety in humans. However, like any drug, some people might experience side effects. Ongoing research will help determine the best dose to minimize potential risks.

Prospective trial participants should discuss any concerns or questions with the study team or their doctor. They can provide more details about what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for pancreatic cancer?

Researchers are excited about this trial because it explores a new imaging technique for pancreatic cancer surgery using Panitumumab-IRDye800. Unlike standard treatments like chemotherapy and radiation, this method aims to improve surgical outcomes by making cancer cells more visible during surgery. This imaging technique uses a special dye that binds specifically to cancer cells, potentially allowing surgeons to see and remove tumors more accurately. The hope is that this will lead to fewer cancer cells being left behind, reducing the chance of recurrence and improving long-term outcomes for patients.

What evidence suggests that Panitumumab-IRDye800 is effective for imaging pancreatic cancer?

Research has shown that panitumumab-IRDye800, administered in varying doses to participants in this trial, can enhance the visibility of pancreatic cancer during surgery. In earlier studies, this combination of a drug and a dye successfully highlighted pancreatic tumors. Panitumumab targets a protein called EGFR, commonly found on cancer cells, aiding surgeons in seeing the tumors more clearly. Studies in other cancers, such as colorectal and oropharyngeal, have also demonstrated the effectiveness of this method. These findings suggest it could be a valuable tool in pancreatic cancer surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Eben Rosenthal

Principal Investigator

Stanford University

George Poultsides

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals with suspected or confirmed pancreatic adenocarcinoma who are planning surgery to remove the cancer. They should have a life expectancy of over 12 weeks, be relatively active (able to care for themselves), and have normal blood counts and electrolyte levels. It's not suitable for those with certain health conditions that aren't listed here.

Inclusion Criteria

Hemoglobin >= 9 gm/dL

Magnesium > the lower limit of normal per institution normal lab values

I have been diagnosed with pancreatic cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a loading dose of panitumumab followed by panitumumab-IRDye800, and undergo surgical resection with intraoperative imaging

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Panitumumab
• Panitumumab-IRDye800

Trial Overview The study is testing Panitumumab-IRDye800, which combines an antibody drug with a special dye visible using a camera during surgery. The goal is to see if this makes cancer cells easier to find and remove during operations in patients with pancreatic cancer.

How Is the Trial Designed?

Group I: Cohort 2- Dose Expansion Experimental Treatment 3 Interventions

Cohort 2 will receive the optimal dose of Panitumumab-IRDye800 as determined in Cohort 1

Group II: Cohort 1d Experimental Treatment 3 Interventions

Cohort 1d will receive a 50 mg dose of Panitumumab IRDye800 and no test/loading dose. A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices

Group III: Cohort 1c Experimental Treatment 3 Interventions

Cohort 1c will receive 75 mg of Panitumumab IRDye800 with a 100 mg unlabeled test/loading dose of Panitumumab.A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices

Group IV: Cohort 1b Experimental Treatment 3 Interventions

Cohort 1b will receive 50 mg of Panitumumab IRDye800 with a 100 mg unlabeled test/loading dose of Panitumumab. A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices

Group V: Cohort 1a Experimental Treatment 3 Interventions

A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. Cohort 1a will receive 25 mg of Panitumumab IRDye800 with a 100 mg unlabeled test/loading dose of Panitumumab. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices

Panitumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Approved in United States as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Who Is Running the Clinical Trial?

Eben Rosenthal

Lead Sponsor

Trials

9

Recruited

200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Panitumumab, an epidermal growth factor receptor inhibitor, is generally well tolerated in Japanese patients with advanced solid tumors, showing a safety profile consistent with that of non-Japanese patients.

Mild-to-moderate dermatologic toxicities are the most common side effects associated with panitumumab, and the report provides a flowchart for managing these skin reactions effectively in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical management of EGFRI dermatologic toxicities: the Japanese perspective. Yamazaki, N., Muro, K.[2018]

Panitumumab is an effective treatment for RAS wild-type metastatic colorectal cancer, approved for use both in combination with chemotherapy and as a standalone therapy for patients who do not respond to chemotherapy.

The review will also discuss the safety profile of panitumumab and its impact on quality of life, along with insights into predictive biomarkers and mechanisms of resistance that can affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of panitumumab treatment on survival and quality of life in patients with RAS wild-type metastatic colorectal cancer. Battaglin, F., Puccini, A., Ahcene Djaballah, S., et al.[2020]

The study successfully produced high-purity (64)Cu-labeled F(ab')2 fragments of the anti-EGFR antibody panitumumab, which showed strong binding affinity to EGFR on pancreatic cancer cells, indicating potential for targeted imaging.

In vivo imaging with microPET/CT demonstrated that these (64)Cu-panitumumab F(ab')2 fragments localized effectively in patient-derived pancreatic cancer xenografts, allowing for clear visualization of tumors at 24 and 48 hours post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MicroPET/CT imaging of patient-derived pancreatic cancer xenografts implanted subcutaneously or orthotopically in NOD-scid mice using (64)Cu-NOTA-panitumumab F(ab')2 fragments. Boyle, AJ., Cao, PJ., Hedley, DW., et al.[2019]

Panitumumab, when combined with chemotherapy, significantly prolongs progression-free survival in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival compared to chemotherapy alone, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: a review of its use in metastatic colorectal cancer. Keating, GM.[2021]

Panitumumab, an anti-EGFR monoclonal antibody, significantly improves progression-free survival when combined with chemotherapy in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival when combined with certain chemotherapy regimens, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. Keating, GM.[2018]

Panitumumab is a well-tolerated fully human monoclonal antibody that targets the epidermal growth factor receptor, showing efficacy in various cancers, particularly metastatic colorectal cancer, without the need for premedications or significant infusion reactions.

The most common side effect is a mild to moderate rash, similar to other EGFR-targeting agents, and ongoing studies are exploring its use in combination with standard treatments like FOLFOX and novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of panitumumab in the management of metastatic colorectal cancer. Saif, MW., Cohenuram, M.[2018]

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]

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]

Panitumumab (Vectibix) was evaluated in a trial with 463 patients suffering from advanced colorectal cancer, showing a mean progression-free survival (PFS) of 96 days compared to 60 days for those receiving only best supportive care, indicating a significant benefit in delaying disease progression.

Despite the improvement in PFS and an objective response rate of 8%, there was no difference in overall survival between the treatment groups, leading to accelerated approval by the FDA with the requirement for further confirmation of clinical benefit for full approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Giusti, RM., Shastri, K., Pilaro, AM., et al.[2020]

In a phase 2 study involving 148 patients with metastatic colorectal cancer, panitumumab demonstrated a 9% overall response rate and a median progression-free survival of 14 weeks, indicating its efficacy as a treatment option for patients who had previously failed other therapies.

Panitumumab was generally well tolerated, with manageable side effects; 95% of patients experienced skin toxicity, but only 5% had severe reactions, suggesting that while dermatologic issues are common, they are not typically severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Hecht, JR., Patnaik, A., Berlin, J., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32416764/

Tumour-specific fluorescence-guided surgery for pancreatic ... This study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is ...

2. withpower.com withpower.com/trial/panitumumab-irdye800-imaging-for-pancreatic-cancer-fae27

Panitumumab-IRDye800 Imaging for Pancreatic Cancer Panitumumab, a component of Panitumumab-IRDye800, has shown effectiveness in treating other cancers like colorectal cancer by targeting EGFR (a protein that ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/30/18/4016/747459/Interim-Phase-II-Results-Using-Panitumumab

Interim Phase II Results Using Panitumumab-IRDye800CW ... Interim Phase II results using Panitumumab-IRDye800CW during transoral robotic surgery in patients with oropharyngeal cancer.

4. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(20)30123-0/abstract

The future of tumour-specific fluorescence-guided surgery ... Tumour-specific fluorescence-guided surgery for pancreatic cancer using panitumumab-IRDye800CW: a phase 1 single-centre, open-label, single-arm, dose- ...

5. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/p/NCT03384238.html

Panitumumab-IRDye800 in Patients With Pancreatic Cancer ... Panitumumab-IRDye800 is a combination of the antibody drug panitumumab and IRDye800CW, an investigational dye that can be seen using a special camera.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7367758/

Tumor-Specific Fluorescence-Guided Surgery for ... In summary, this first-in-human, dose-escalation study showed that panitumumab-IRDye800CW is safe and feasible to use for fluorescence-guided ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5928904/

Safety of panitumumab-IRDye800CW and cetuximab- ... Panitumumab has about an eight-times stronger and more specific binding to EGFR,. Panitumumab was first approved by the FDA in September 2006 ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125320300881

Articles Tumour-specific fluorescence-guided surgery for ... We present evidence using a fully humanised antibody (panitumumab) labelled with IRDye800CW (panitumumab-IRDye800CW) as an imaging agent for pancreatic ductal ...

9. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/164596

Panitumumab-IRDye800 in Patients With Pancreatic ... This phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 and to see how well it works in finding cancer in ...

10. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(20)30088-1/abstract

Tumour-specific fluorescence-guided surgery for ... To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows ...