Investigational Scan for Breast Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: City of Hope Medical Center
Must be taking: Trastuzumab deruxtecan
Disqualifiers: Immediate intervention, Lung disease, Corneal disease, Cardiac issues
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This clinical trial examines an investigational scan (64Cu-DOTA-trastuzumab positron emission tomography \[PET\]/magnetic resonance imaging \[MRI\]) in imaging patients with HER2+ breast cancer that has spread to the brain (brain metastasis). Diagnostic procedures, such as 64Cu-DOTA-trastuzumab PET/MRI, may help find HER2+ breast cancer that has spread to the brain and determine whether cancer in the brain takes up trastuzumab, which may predict for response to trastuzumab deruxtecan (the standard of care chemotherapy).
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, since the trial involves imaging and not a new treatment, it's possible that you may not need to stop them. Please consult with the trial coordinators for specific guidance.
What data supports the effectiveness of the investigational scan for breast cancer treatment using 64Cu-DOTA-Trastuzumab PET/MRI?
Research shows that 64Cu-DOTA-Trastuzumab PET imaging can effectively detect HER2-positive tumors in breast cancer patients, indicating its potential to help identify appropriate candidates for anti-HER2 therapies. Studies in mice and patients with HER2-positive cancers have demonstrated high uptake of the tracer in tumors, suggesting it can accurately assess HER2 expression and guide treatment decisions.
12345Is 64Cu-DOTA-Trastuzumab safe for humans?
A study on 64Cu-DOTA-Trastuzumab PET imaging in patients with HER2-positive breast cancer aimed to determine its safety, suggesting that there is some safety data available for this treatment in humans.
12678How does the investigational scan for breast cancer differ from other treatments?
The investigational scan for breast cancer uses a radiolabeled version of trastuzumab, a drug that targets HER2, to non-invasively image HER2 expression in tumors. This approach is unique because it allows for the visualization of HER2 status throughout the body, potentially optimizing the use of anti-HER2 therapies by identifying which patients are most likely to benefit from them.
12347Eligibility Criteria
This trial is for adults over 18 with HER2+ breast cancer that has spread to the brain. They must have a certain level of hemoglobin, kidney function, heart function, and blood cell counts. Patients already planning treatment with fam-trastuzumab deruxtecan can join. Those with serious recent heart issues or lung disease needing steroids cannot participate.Inclusion Criteria
I am scheduled to receive fam-trastuzumab deruxtecan treatment.
Your absolute neutrophil count is higher than 1.5 x 10^9 per liter.
I am a woman with HER2 positive breast cancer that has spread to my brain.
+12 more
Exclusion Criteria
I have a lung condition treated with steroids but it's not caused by an infection.
I have a serious eye condition affecting the cornea.
I haven't had a heart attack or serious heart issues in the last 6 months.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive trastuzumab IV on day 0, followed by 64Cu-DOTA-trastuzumab IV and PET/MRI scan on day 1. Repeat brain MRI every 6 weeks for 24 weeks, then every 9 weeks until disease progression. Trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
24 weeks
Multiple visits for MRI and IV administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Participant Groups
The study is testing a new scan combining PET and MRI using a tracer called 64Cu-DOTA-Trastuzumab to see if it's better at detecting HER2+ breast cancer in the brain and predicting response to standard chemotherapy (trastuzumab deruxtecan).
1Treatment groups
Experimental Treatment
Group I: Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)Experimental Treatment5 Interventions
Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Pilot study of HER2 targeted 64 Cu-DOTA-tagged PET imaging in gastric cancer patients. [2023]Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64 Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64 Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or - GC patients.
Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with Cu-labeled trastuzumab PET. [2019]Non-small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of (64)Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with (64)Cu. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/neu overexpression (NCI-H2170) and negative expression (NCI-H520). Imaging of Her2/neu expression was performed in NCI-H2170 tumor-bearing mice with (64)Cu-DOTA-trastuzumab PET and (64)Cu-DOTA-IgG. In vitro studies revealed specific binding of DOTA-trastuzumab in the Her2/neu positive NCI-H2170 cells, while no binding was seen in the Her2/neu negative NCI-H520 cell line. Biodistribution and PET studies revealed a significantly high accumulation of (64)Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 and 48 h post-injection (21.4 +/- 1.4% and 23.2 +/- 5.1% injection dose/gram (% ID/g), respectively). PET imaging of Her2/neu negative NCI-H520 tumors showed much less uptake of (64)Cu-DOTA-trastuzumab (4.0% ID/g). The NCI-H2170 tumor uptake of (64)Cu-DOTA-trastuzumab was significantly higher than that of (64)Cu-DOTA-IgG (P
Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. [2022]Women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are candidates for treatment with the anti-HER2 antibody trastuzumab. Assessment of HER2 status in recurrent disease is usually made by core needle biopsy of a single lesion, which may not represent the larger tumor mass or other sites of disease. Our long-range goal is to develop PET of radiolabeled trastuzumab for systemically assessing tumor HER2 expression and identifying appropriate use of anti-HER2 therapies. The purpose of this study was to evaluate PET/CT of (64)Cu-DOTA-trastuzumab for detecting and measuring tumor uptake of trastuzumab in patients with HER2-positive metastatic breast cancer.
Tumor Uptake of 64Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer. [2021]The goal of this study was to characterize the relationship between tumor uptake of 64Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUVmax Average intrapatient SUVmax (<SUVmax>pt) was compared between HER2+ and HER2- patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median <SUVmax>pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients (P < 0.005 either day). The distributions of <SUVmax>pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease (P < 0.005 and 0.001, respectively, on days 1 and 2). Conclusion: By 1 d after injection, uptake of 64Cu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for 64Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.
[(64) Cu]-labelled trastuzumab: optimisation of labelling by DOTA and NODAGA conjugation and initial evaluation in mice. [2021]The human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-30% of all breast cancer cases, leading to increased cell proliferation, growth and migration. The monoclonal antibody, trastuzumab, binds to HER2 and is used for treatment of HER2-positive breast cancer. Trastuzumab has previously been labelled with copper-64 by conjugation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. The aim of this study was to optimise the (64) Cu-labelling of DOTA-trastuzumab and as the first to produce and compare with its 1,4,7-triazacyclononane, 1-glutaric acid-5,7 acetic acid (NODAGA) analogue in a preliminary HER2 tumour mouse model. The chelators were conjugated to trastuzumab using the activated esters DOTA mono-N-hydroxysuccinimide (NHS) and NODAGA-NHS. (64) Cu-labelling of DOTA-trastuzumab was studied by varying the amount of DOTA-trastuzumab used, reaction temperature and time. Full (64) Cu incorporation could be achieved using a minimum of 10-µg DOTA-trastuzumab, but the fastest labelling was obtained after 15 min at room temperature using 25 µg of DOTA-trastuzumab. In comparison, 80% incorporation was achieved for (64) Cu-labelling of NODAGA-trastuzumab. Both [(64) Cu]DOTA-trastuzumab and [(64) Cu]NODAGA-trastuzumab were produced after purification with radiochemical purities of >97%. The tracers were injected into mice with HER2 expressing tumours. The mice were imaged by positron emission tomography and showed high tumour uptake of 3-9% ID/g for both tracers.
Development and preclinical studies of 64Cu-NOTA-pertuzumab F(ab')2 for imaging changes in tumor HER2 expression associated with response to trastuzumab by PET/CT. [2019]We previously reported that microSPECT/CT imaging with 111In-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab')2 of pertuzumab modified with NOTA chelators for complexing 64Cu. The effect of the administered mass (5-200 µg) of 64Cu-NOTA-pertuzumab F(ab')2 was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts. Biodistribution studies were performed in non-tumor bearing Balb/c mice to predict radiation doses to normal organs in humans. Serial PET/CT imaging was conducted on mice engrafted with HER2-positive and trastuzumab-sensitive BT-474 or trastuzumab-insensitive SK-OV-3 xenografted mice treated with weekly doses of trastuzumab. There were no significant effects of the administered mass of 64Cu-NOTA-pertuzumab F(ab')2 on tumor or normal tissue uptake. The predicted total body dose in humans was 0.015 mSv/MBq, a 3.3-fold reduction compared to 111In-labeled pertuzumab. MicroPET/CT images revealed specific tumor uptake of 64Cu-NOTA-pertuzumab F(ab')2 at 24 or 48 h post-injection in mice with SK-OV-3 tumors. Image analysis of mice treated with trastuzumab showed 2-fold reduced uptake of 64Cu-NOTA-pertuzumab F(ab')2 in BT-474 tumors after 1 week of trastuzumab normalized to baseline, and 1.9-fold increased uptake in SK-OV-3 tumors after 3 weeks of trastuzumab, consistent with tumor response and resistance, respectively. We conclude that PET/CT imaging with 64Cu-NOTA-pertuzumab F(ab')2 detected changes in HER2 expression in response to trastuzumab while delivering a lower total body radiation dose compared to 111In-labeled pertuzumab.
Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer. [2021]68Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-F(ab')2-trastuzumab [68Ga-DOTA-F(ab')2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA-F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously.
64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer. [2022]The purpose of this study was to determine the safety, distribution, internal dosimetry, and initial human epidermal growth factor receptor 2 (HER2)-positive tumor images of (64)Cu-DOTA-trastuzumab in humans.