89Zr-DFO-nimotuzumab for Lung and Colorectal Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of Saskatchewan
No Placebo Group
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?Over-expression of Epidermal Growth Factor Receptor (EGFR) on cells occurs in all aggressive cancers of epithelial origin. Existing tests for monitoring EGFR expression are invasive and not reliable. There needs to be a better way to measure EGFR expression in cancerous tumors to better tailor cancer treatments.
This clinical trial aims to demonstrate the feasibility of imaging cancers that express EGFR using 89Zr-DFO-nimotuzumab and Positron Emission Tomography (PET)/Computerized Tomography (CT). By non-invasively imaging the status of EGFR, 89Zr-DFO-nimotuzumab could be used to assist in the identification of patients who are likely to respond to anti-EGFR treatments, including nimotuzumab. The hypothesis is that 89Zr-DFO-nimotuzumab will accumulate to tumors over-expressing EGFR making them visible when imaged with PET/CT. This hypothesis will be tested in this study, along with the optimal imaging time and diagnostic ability.
Is 89Zr-DFO-nimotuzumab a promising drug for lung and colorectal cancer?Yes, 89Zr-DFO-nimotuzumab is a promising drug for lung and colorectal cancer. It targets a protein called EGFR, which is often found in high amounts in these cancers. This drug helps doctors see and track the cancer using special imaging, and it has shown positive results in studies, including complete tumor remission in some cases.13459
What safety data is available for 89Zr-DFO-nimotuzumab or nimotuzumab?Nimotuzumab has been evaluated for safety in various studies. In a trial for advanced nonsmall cell lung cancer, adverse drug reactions were monitored. In the treatment of inoperable esophageal tumors, the frequency, seriousness, causality, and severity of adverse events were assessed. In a study involving severe and critical COVID-19 patients, nimotuzumab was well-tolerated with mild or moderate adverse events in 19 out of 1,151 patients. These studies suggest that nimotuzumab is generally safe with manageable adverse effects.24789
What data supports the idea that 89Zr-DFO-nimotuzumab for Lung and Colorectal Cancer is an effective drug?The available research shows that nimotuzumab, when used in combination with chemotherapy, has shown promise in treating advanced non-small cell lung cancer (NSCLC). In one study, nimotuzumab was combined with chemotherapy and resulted in improved outcomes for patients. Another study highlighted that nimotuzumab, when used with chemoradiotherapy, was effective and well-tolerated in patients with locally advanced NSCLC. Additionally, in colorectal cancer, nimotuzumab was part of a treatment that led to complete remission in some cases. These findings suggest that nimotuzumab can be an effective drug for treating lung and colorectal cancer.12469
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had any previous treatment with anti-EGFR antibodies.
Eligibility Criteria
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.
My cancer has a tumor or spread that is at least 1.5 cm big.
My cancer is EGFR-positive, as confirmed by a specialist.
I am between 18 and 80 years old.
I can take care of myself and perform light activities.
Exclusion Criteria
I cannot stay still for 60 minutes during a PET scan.
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Establish Imaging TimeExperimental Treatment1 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 DoseExperimental Treatment1 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 QualityExperimental Treatment1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Royal University HospitalSaskatoon, Canada
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Who is running the clinical trial?
University of SaskatchewanLead Sponsor
References
The emerging role of nimotuzumab in the treatment of non-small cell lung cancer. [2021]Current non-small cell lung cancer (NSCLC) chemotherapy and radiotherapy regimens, although showing definite survival benefit, still leave patients with a disappointing 15% 5-year overall survival rate. Because of the need to improve traditional outcomes, research has focused on identifying specific tumorigenic pathways that may serve as therapeutic targets. The most successful strategies to date are those aimed at the epidermal growth factor receptor (EGFR), which is found to be upregulated in 40%-80% of NSCLC. Several tyrosine kinase inhibitors and monoclonal antibodies (mAbs) have been developed that inhibit the EGFR receptor and have demonstrated clinical benefit in trials as single agents and in combination regimens. Here we discuss one such agent, the mAb nimotuzumab, the background of its development, its clinical experience in NSCLC thus far, and the rationale for expanding its use to other NSCLC treatment settings.
A clinical trial on docetaxel and carboplatin therapy with or without nimotuzumab for the treatment of advanced nonsmall cell lung cancer. [2018]To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) through progress-free survival, changes in tumor marker expression and adverse drug reactions.
[Nimotuzumab Combined with Chemotherapy as Second- or Later-line in the Treatment of Advanced Lung Squamous Cell Carcinoma]. [2018]Epidermal growth factor receptor (EGFR) is commonly overexpressed in lung squamous cell carcinoma and has been associated with impaired prognosis. The aim of this study was to observe the efficacy and safety of nimotuzumab, a anti-EGFR monoclonal antibody, combined with chemotherapy as second- or later-line in the treatment of advanced lung squamous cell carcinoma.
89Zr-nimotuzumab for immunoPET imaging of epidermal growth factor receptor I. [2022]Label="RATIONALE" NlmCategory="BACKGROUND">Epidermal growth factor receptor (EGFR) upregulation is associated with enhanced proliferation and drug resistance in a number of cancers. Nimotuzumab is a humanized monoclonal antibody with high affinity for EGFR. The objective of this study was to determine if 89Zr-DFO-nimotuzumab could be suitable for human use as a PET probe for quantifying EGFR in vivo.
89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo. [2020]89Zr immuno-PET continues to be assessed in numerous clinical trials. This report evaluates the use of 89Zr-chloride in the radiolabeling of monoclonal antibodies conjugated with desferrioxamine B (DFO), describes its effects on radiopharmaceutical reactivity toward antigen, and offers guidance on how to ensure long-term stability and purity. Methods:89Zr-DFO-trastuzumab and 89Zr-DFO-cetuximab were prepared using 89ZrCl4 The stability of each was evaluated for 7 d in 20 mM histidine/240 mM sucrose buffer, 0.25 M sodium acetate (NaOAc) buffer containing 5 mg·mL-1n-acetyl-l-cysteine (NAC), or 0.25 M NaOAc containing 5 mg·mL-1 l-methionine (L-MET). To assess antigen reactivity, 89Zr-DFO-trastuzumab was evaluated using the Lindmo method and tested in PET/CT imaging of mouse models of human epidermal growth factor receptor 2-positive or -negative lung cancer. Results: Using 89ZrCl4, 89Zr-DFO-trastuzumab and 89Zr-DFO-cetuximab were prepared with increased specific activity and retained purities of 95% after 3 d when formulated in NaOAc buffer containing L-MET. Based on Lindmo analysis and small-animal PET/CT imaging, 89Zr-DFO-trastuzumab remained reactive toward antigen after being prepared with 89ZrCl4Conclusion:89ZrCl4 facilitated the radiosynthesis of 89Zr immuno-PET agents with increased specific activity. L-MET enhanced long-term solution stability better than all other formulations examined, and 89Zr-DFO-trastuzumab remained reactive toward antigen. Although further evaluation is necessary, these initial results suggest that 89ZrCl4 may be useful in immuno-PET radiochemistry as radiolabeled monoclonal antibodies are increasingly integrated into precision medicine strategies.
Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer. [2021]We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer.
Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario. [2022]EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several cancer indications. An expanded access study was conducted to evaluate the safety and recovery rate of severe and critical patients with confirmed SARS-CoV-2 infection, treated with nimotuzumab in combination with the standard of care in the real-world scenario. The antibody was administered as an intravenous infusions every 72 h, up to 5 doses. In order to assess the impact of nimotuzumab, the recovery rate was compared with a paired retrospective cohort. Control patients received standard treatment according the national protocol but not nimotuzumab. Overall, 1,151 severe or critical patients received nimotuzumab in 21 hospitals of Cuba. Median age was 65 and 773 patients had at least one comorbidity. Nimotuzumab was very well-tolerated and mild or moderate adverse events were detected in 19 patients. 1,009 controls matching with the nimotuzumab patients, were selected using a "propensity score" method. The 14-day recovery rate of the nimotuzumab cohort was 72 vs. 42% in the control group. Controls had a higher mortality risk (RR 2.08, 95% CI: 1.79, 2.38) than the nimotuzumab treated patients. The attributable fraction was 0.52 (95% CI: 0.44%; 0.58), and indicates the proportion of deaths that were prevented with nimotuzumab. Our preliminary results suggest that nimotuzumab is a safe antibody that can reduce the mortality of severe and critical COVID-19 patients.
Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin. [2022]Label="Background" NlmCategory="UNASSIGNED">Nimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor. It was approved in Cuba for the indication of inoperable malignant tumors of the esophagus of epithelial origin. The purpose of this study was to evaluate the safety, overall and progression-free survival, clinical response, and quality of life, in adult patients with inoperable esophageal tumors of epithelial origin treated with nimotuzumab in a practical context. Material and Methods. The number of patients who developed adverse events was determined, and the frequency, seriousness, causality, and severity of these adverse events were determined. It also determined the median of survival and progression-free survival and rates at 12 and 24 months and the quality of life.
Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. [2022]Matuzumab and nimotuzumab are anti-EGFR monoclonal antibodies that bind to different epitopes of domain III of EGFR. We developed 89Zr-matuzumab as a PET probe for diagnosis/monitoring of response to treatment of a noncompeting anti-EGFR nimotuzumab antibody drug conjugate (ADC) using mouse colorectal cancer (CRC) xenografts. We developed 89Zr-matuzumab and performed quality control in EGFR-positive DLD-1 cells. The KD of matuzumab, DFO-matuzumab and 89Zr-matuzumab in DLD-1 cells was 5.9, 6.2 and 3 nM, respectively. A competitive radioligand binding assay showed that 89Zr-matuzumab and nimotuzumab bound to noncompeting epitopes of EGFR. MicroPET/CT imaging and biodistribution of 89Zr-matuzumab in mice bearing EGFR-positive xenografts (HT29, DLD-1 and MDA-MB-231) showed high uptake that was blocked with pre-dosing with matuzumab but not with the noncompeting binder nimotuzumab. We evaluated nimotuzumab-PEG6-DM1 ADC in CRC cells. IC50 of nimotuzumab-PEG6-DM1 in SNU-C2B, DLD-1 and SW620 cells was dependent on EGFR density and was up to five-fold lower than that of naked nimotuzumab. Mice bearing the SNU-C2B xenograft were treated using three 15 mg/kg doses of nimotuzumab-PEG6-DM1, and 89Zr-matuzumab microPET/CT was used to monitor the response to treatment. Treatment resulted in complete remission of the SNU-C2B tumor in 2/3 mice. Matuzumab and nimotuzumab are noncompeting and can be used simultaneously.