89Zr-DFO-nimotuzumab for Lung and Colorectal Cancer

Overseen By Rajan Rakheja, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Saskatchewan

Must not be taking: Anti-EGFR antibodies

Disqualifiers: Pregnancy, Nursing, PET intolerance, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to visualize certain cancer cells more clearly using a special treatment called 89Zr-DFO-nimotuzumab, an imaging agent, along with advanced imaging techniques. It targets cancers with high levels of a protein called EGFR, common in aggressive lung and colorectal cancers. The goal is to make these cancer cells visible with scans, aiding doctors in selecting the best treatments for patients. Individuals with EGFR-positive cancers who have not received treatments targeting EGFR may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does require that participants have not previously been treated with anti-EGFR antibodies.

What prior data suggests that 89Zr-DFO-nimotuzumab is safe for imaging EGFR-expressing cancers?

Research has shown that nimotuzumab, a key component of 89Zr-DFO-nimotuzumab, has been tested for safety and effectiveness. When combined with chemotherapy, nimotuzumab demonstrated a safety profile similar to chemotherapy alone, with no unexpected side effects and general tolerability.

Although 89Zr-DFO-nimotuzumab is not yet approved for imaging, nimotuzumab has been safely used in other contexts. This study examines its use in imaging cancers, particularly those with high levels of EGFR, a protein linked to aggressive tumors. As this trial is in the early stages, the primary goal is to assess the safety of the imaging process.

Participants will be closely monitored for any side effects for up to 30 days after receiving the treatment. This careful observation ensures safety and checks for any adverse reactions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for lung and colorectal cancer, which typically involve chemotherapy, radiation, or surgery, 89Zr-DFO-nimotuzumab offers a targeted approach. This investigational treatment uses a radiolabeled antibody to specifically target cancer cells, potentially improving diagnostic imaging and allowing for more precise treatment strategies. Researchers are excited because it could offer a clearer picture of cancer spread and response, helping tailor treatments more effectively. Additionally, the unique use of the radioactive zirconium isotope (89Zr) in the antibody might provide earlier detection of cancerous activity compared to current methods.

What evidence suggests that 89Zr-DFO-nimotuzumab is effective for imaging EGFR in lung and colorectal cancer?

Research has shown that nimotuzumab, a treatment targeting the Epidermal Growth Factor Receptor (EGFR), can improve cancer patient outcomes when combined with other treatments. Other EGFR-targeting drugs have also succeeded in clinical settings. One study found that patients receiving nimotuzumab with chemotherapy lived without cancer progression for about 9.89 months, compared to 7.86 months for those with only chemotherapy. This suggests nimotuzumab can slow cancer progression. In this trial, researchers focus on using a version of nimotuzumab called 89Zr-DFO-nimotuzumab for imaging. Participants in different arms will receive varying doses to establish optimal imaging conditions. This could help identify tumors with EGFR, allowing for more personalized treatment plans. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with EGFR-positive lung or colorectal cancer who haven't been treated with anti-EGFR antibodies. They must be in good health, not pregnant or nursing, able to consent, and have a tumor size of at least 1.5 cm. It's not suitable for those unable to undergo a 60-minute PET scan.

Inclusion Criteria

I have never been treated with anti-EGFR antibodies.

Able to give informed consent.

My cancer has a tumor or spread that is at least 1.5 cm big.

Exclusion Criteria

I cannot stay still for 60 minutes during a PET scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an i.v. injection of 89Zr-DFO-nimotuzumab and undergo imaging at multiple time points

1 week

4 visits (in-person)

Follow-up

Participants are monitored for any adverse events until day 30 post administration

3 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 89Zr-DFO-nimotuzumab

Trial Overview The study tests if the drug 89Zr-DFO-nimotuzumab can help image cancers expressing EGFR using PET/CT scans non-invasively. Participants will receive either a high (50 mg) or low (1 mg) dose of the drug to determine its effectiveness and optimal imaging time.

How Is the Trial Designed?

Group I: Establish Imaging Time Experimental Treatment 1 Intervention

Participants will receive an i.v. injection of 50 mg 2 mCi 89Zr-DFO-nimotuzumab. Participants will undergo imaging at four different time points till day 7 after infusion. Vitals, blood sample and urine sample will be collected every time before imaging. Participants will be followed up for any adverse event until day 30 post administration

Group II: Establish Cold Dose Experimental Treatment 1 Intervention

Participants will receive an i.v. injection of 1 mg 2 mCi 89Zr-DFO-nimotuzumab. Participants will undergo imaging at four different time points till day 7 after infusion. Vitals, blood sample and urine sample will be collected every time before imaging. Participants will be followed up for any adverse event until day 30 post administration

Group III: Diagnostic Quality Experimental Treatment 1 Intervention

Participants will receive an i.v. injection of 50 mg 2 mCi 89Zr-DFO-nimotuzumab. Participants will undergo imaging once at the best time calculated from arm 1 participants. Vitals, blood sample and urine sample will be collected before imaging. Participants will be followed up for any adverse event until day 30 post administration

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

Published Research Related to This Trial

Current treatments for non-small cell lung cancer (NSCLC) have a low 5-year survival rate of only 15%, highlighting the need for improved therapies targeting specific tumor pathways.

Nimotuzumab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has shown clinical benefits in NSCLC and may be expanded for use in additional treatment settings due to its effectiveness against the upregulated EGFR found in 40%-80% of NSCLC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of nimotuzumab in the treatment of non-small cell lung cancer. Boland, W., Bebb, G.[2021]

In a study of 13 patients with advanced lung squamous cell carcinoma, nimotuzumab combined with chemotherapy showed an overall response rate of 23.1%, with a higher response rate of 33.3% in patients who were EGFR positive.

The treatment was generally well-tolerated, with only mild non-hematological toxicities and moderate hematological toxicities observed in 23.1% of patients, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nimotuzumab Combined with Chemotherapy as Second- or Later-line in the Treatment of Advanced Lung Squamous Cell Carcinoma]. Luo, Y., Li, J., Wang, Y., et al.[2018]

In a phase 2 trial involving 40 patients with unresectable locally advanced non-small-cell lung cancer, the addition of nimotuzumab to chemoradiotherapy was well tolerated, achieving a high treatment completion rate of 87.2% without severe adverse effects.

The treatment showed promising efficacy, with an objective response rate of 69.2% and a 5-year overall survival rate of 58.4%, particularly benefiting patients with squamous cell carcinoma, who had a 5-year progression-free survival rate of 50.0%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer. Yamamoto, N., Harada, H., Okamoto, I., et al.[2021]

In a study involving 1,151 severe or critical COVID-19 patients treated with nimotuzumab, the recovery rate was significantly higher at 72% compared to 42% in a matched control group, indicating its potential efficacy in improving patient outcomes.

Nimotuzumab was well-tolerated with only mild to moderate adverse events reported in 19 patients, suggesting it is a safe treatment option for severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario. Diaz, H., Jiménez, J., Hernández, A., et al.[2022]

89Zr-matuzumab was developed as a PET imaging probe to monitor treatment responses in colorectal cancer, showing high uptake in EGFR-positive tumors and confirming its binding to noncompeting epitopes of EGFR.

The nimotuzumab-PEG6-DM1 antibody-drug conjugate demonstrated significantly improved efficacy in targeting colorectal cancer cells, achieving complete tumor remission in 2 out of 3 mice treated, indicating its potential as an effective therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. Tikum, AF., Nambisan, AK., Ketchemen, JP., et al.[2022]

89Zr-DFO-nimotuzumab, a PET probe targeting EGFR, demonstrated high tumor uptake in mice with EGFR-positive tumors, indicating its potential effectiveness for imaging in cancer diagnostics.

The study showed that 89Zr-DFO-nimotuzumab has a low projected human effective dose and no significant normal tissue toxicity, suggesting it is safe for potential use in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-nimotuzumab for immunoPET imaging of epidermal growth factor receptor I. Chekol, R., Solomon, VR., Alizadeh, E., et al.[2022]

The use of 89ZrCl4 for radiolabeling monoclonal antibodies like trastuzumab and cetuximab resulted in high specific activity and maintained over 95% purity for at least 3 days when formulated with L-methionine, indicating effective preparation for immuno-PET imaging.

89Zr-DFO-trastuzumab demonstrated sustained reactivity toward its target antigen in PET/CT imaging of lung cancer models, suggesting its potential utility in precision medicine for cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo. Pandya, DN., Bhatt, NB., Almaguel, F., et al.[2020]

In a study of 59 patients with advanced nonsmall cell lung cancer, the combination of nimotuzumab with chemotherapy (docetaxel and carboplatin) significantly prolonged progression-free survival by 1 month compared to chemotherapy alone.

Nimotuzumab was well tolerated, with only mild skin rashes reported, indicating a favorable safety profile while potentially enhancing the effectiveness of treatment as shown by significant decreases in certain tumor markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial on docetaxel and carboplatin therapy with or without nimotuzumab for the treatment of advanced nonsmall cell lung cancer. Qi, D., Cui, Y., Wang, Q., et al.[2018]

Nimotuzumab, a monoclonal antibody targeting the epidermal growth factor receptor, was found to be safe for patients with inoperable esophageal tumors, with only 1.3% experiencing serious adverse events, mostly mild to moderate in severity.

Patients treated with nimotuzumab alongside chemotherapy and radiotherapy achieved a median overall survival of 12.2 months and a median progression-free survival of 7.8 months, indicating improved survival outcomes and quality of life compared to those not receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin. González Fernández, S., Amador García, Y., Boris Porras, LG., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-colorectal-neoplasms-1-2020-16644

89Zr-DFO-nimotuzumab for Lung and Colorectal Cancer Studies have demonstrated that nimotuzumab can improve outcomes when combined with other treatments, and similar drugs targeting EGFR have shown clinical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7113702/

Clinical efficacy and safety of nimotuzumab plus ... Nimotuzumab combined with chemotherapy had similar efficacy and safety to chemotherapy alone in patients with ACRC.

3. trialx.com trialx.com/clinical-trials/listings/237465/evaluation-of-89zr-dfo-nimotuzumab-for-non-invasive-imaging-of-egfr-cancers-by-positron-emission-tomography-pet/

Evaluation of 89Zr-DFO-nimotuzumab for Non-invasive ... This clinical trial aims to demonstrate the feasibility of imaging cancers that express EGFR using 89Zr-DFO-nimotuzumab and Positron Emission ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e15009

Clinical efficacy and safety evaluation of nimotuzumab ... The median progression-free survival (PFS) was 9.89 months in the combined treatment group and 7.86 months in the chemotherapy alone group, respectively. The ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04459065

Evaluation of IRDye800CW-nimotuzumab in Lung Cancer ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5908310/

89Zr-nimotuzumab for immunoPET imaging of epidermal ... Epidermal growth factor receptor (EGFR) upregulation is associated with enhanced proliferation and drug resistance in a number of cancers.