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

Trial Summary

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 data supports the effectiveness of the drug Panitumumab-IRDye800 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 helps cancer cells grow). Additionally, Panitumumab-IRDye800 has been shown in studies to effectively highlight tumors in mice, suggesting it could help doctors see pancreatic cancer better during surgery. ^{1 2 3 4 5}

Is Panitumumab-IRDye800 safe for use in humans?

Panitumumab, also known as Vectibix, has been used safely in humans for treating certain types of cancer, like colorectal cancer. The most common side effects are mild-to-moderate skin issues, which are typical for drugs in its class. Overall, it has an acceptable safety profile when used alone or with other treatments. ^{1 6 7 8 9}

What makes the drug Panitumumab-IRDye800 unique for pancreatic cancer treatment?

Panitumumab-IRDye800 is unique because it combines the cancer-targeting ability of panitumumab with a fluorescent dye, allowing doctors to visually identify and target EGFR-expressing tumors during surgery, which is not a feature of standard pancreatic cancer treatments. ^{1 2 3 5 10}

What is the purpose of this trial?

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 patients with pancreatic cancer who are undergoing surgery. Panitumumab-IRDye800 is a combination of the antibody drug panitumumab and IRDye800CW, an investigational dye that can be seen using a special camera. Panitumumab-IRDye800 may attach to tumor cells and make them more visible during surgery in patients with pancreatic cancer.

Research Team

Eben Rosenthal

Principal Investigator

Stanford University

George Poultsides

Principal Investigator

Stanford University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. [2018]

2. United States 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. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Role of panitumumab in the management of metastatic colorectal cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of panitumumab-IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers. [2020]

6. United States 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. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical management of EGFRI dermatologic toxicities: the Japanese perspective. [2018]

9. New Zealand 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. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. [2021]