64Cu-LNTH-1363S for Sarcoma and Gastrointestinal Cancer
(PHANTOM Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Lantheus Medical Imaging
Must not be taking: QT prolonging drugs
Disqualifiers: Pregnancy, Breastfeeding, Heart failure, others
No Placebo Group
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This is a multicenter, open-label, prospective Phase 1/2a study to assess safety and tolerability, establish dosimetry and to identify an optimal imaging dose (radioactivity and mass dose) and imaging time window of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent) and to compare its imaging biodistribution with FAP expression by immunohistochemistry (IHC) in patients with sarcomas or GIT cancers. The study will be conducted in 2 parts (Part 1 and Part 2).
Do I need to stop my current medications to join the trial?
The trial information does not specify whether you need to stop taking your current medications. However, if you are taking medications known to cause QT prolongation, you may be excluded from the trial.
What data supports the effectiveness of the drug 64Cu-LNTH-1363S for sarcoma and gastrointestinal cancer?
Research shows that fibroblast activation protein inhibitors (FAPIs), like those used in 64Cu-LNTH-1363S, have been effective in improving imaging contrast in sarcoma and gastrointestinal cancer. Studies with similar FAPI-based imaging agents have demonstrated promising results in diagnosing and managing these cancers, suggesting potential effectiveness for 64Cu-LNTH-1363S.
12345How is the drug 64Cu-LNTH-1363S unique for treating sarcoma and gastrointestinal cancer?
64Cu-LNTH-1363S is unique because it uses copper-64, a radioactive form of copper, to help visualize cancer cells through PET/CT imaging. This drug targets cancer cells by exploiting their increased uptake of copper, which is essential for their growth, making it a novel approach compared to traditional imaging methods.
678910Eligibility Criteria
This trial is for adults with certain types of sarcoma or gastrointestinal cancers, like esophageal, colorectal, stomach, and pancreatic cancer. Participants must have metastatic sarcoma confirmed by medical tests and adequate kidney function. Women who can bear children and men able to father a child must use effective contraception.Inclusion Criteria
I am a man who can father children and agree to use contraception and not donate sperm during and for 28 days after the study.
I am eligible for Part 1 of the study.
I am 18 or older and have given my written consent.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Up to 2 weeks
Intervention
Participants receive 64Cu-LNTH-1363S imaging agent and undergo PET/CT scans to determine biodistribution and dosimetry
1 day
1 visit (in-person)
Safety Follow-up
Participants are monitored for safety and tolerability, including cardiac safety and adverse events
7 days
1 visit (in-person or virtual)
Scheduled Surgery and IHC Sample Collection
Participants undergo surgery for IHC sample collection to correlate imaging results with FAP expression
Up to 60 days post-intervention
Follow-up
Participants are monitored for safety and effectiveness after the intervention and surgery
4 weeks
Participant Groups
The study is testing the safety and optimal imaging dose of a new PET/CT scan agent called 64Cu-LNTH-1363S in two parts. It aims to see how well this agent shows up on scans compared to the actual presence of FAP (a protein) in tumors.
2Treatment groups
Experimental Treatment
Group I: Experimental Part 2Experimental Treatment1 Intervention
Part 2 will evaluate 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent) correlation with FAP expression measured by IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic, operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric, pancreatic, colorectal) planned for surgery within 60 days (from study imaging).
Group II: Experimental Part 1Experimental Treatment1 Intervention
Six patients with metastatic sarcoma will receive 8 ± 1 millicurie (mCi) (\~50 μg mass dose) of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent).
Six patients with metastatic sarcoma will receive 8 ± 1 millicurie (mCi) (\~90 μg mass dose) of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent).
64Cu-LNTH-1363S is already approved in United States for the following indications:
🇺🇸 Approved in United States as 64Cu-LNTH-1363S for:
- Sarcoma
- Esophageal Cancer
- Gastric Cancer
- Pancreatic Cancer
- Colorectal Cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's Hospital Medical CenterCincinnati, OH
UC Irvine Health - Chao Family Comprehensive Cancer CenterOrange, CA
Stanford Hospital & ClinicsStanford, CA
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Who Is Running the Clinical Trial?
Lantheus Medical ImagingLead Sponsor
References
Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT. [2022]Label="PURPOSE">A high expression of fibroblast activation protein (FAP) was observed in multiple sarcomas, indicating an enormous potential for PET/CT using 68Ga-radiolabeled inhibitors of FAP (FAPI). Therefore, this retrospective study aimed to evaluate the role of the novel hybrid imaging probe for sarcomas as a first clinical evaluation.
Gallium-68-labeled fibroblast activation protein inhibitor PET in gastrointestinal cancer: insights into diagnosis and management. [2022]Label="PURPOSE">Gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) is an emerging promising tumor tracer. This study aims to evaluate the diagnostic efficiency of 68Ga-FAPI PET in gastrointestinal cancer, and to determine its potential impact on clinical management.
Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma. [2022]Label="PURPOSE">We aimed to evaluate the value of [68 Ga]Ga-DOTA-FAPI-04 PET/CT for the diagnosis of recurrent soft tissue sarcoma (STS), compared with [18F]FDG PET/CT.
Synthesis and Preclinical Evaluation of a Novel FAPI-04 Dimer for Cancer Theranostics. [2023]Overexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts in a wide variety of tumors enables a highly selective targeting strategy using FAP inhibitors (FAPIs). Quinoline-based FAPIs labeled with radionuclides have been widely developed for tumor-targeted nuclear medicine imaging. However, the short retention time of FAPIs at the tumor site limits their application in radionuclide therapy. In this study, a novel FAPI-04 dimer was synthesized and labeled with radionuclides to prolong the retention time in tumors for imaging and therapy. To prepare the FAPI-04 dimer complex, DOTA-Suc-Lys-(FAPI-04)2, we used Fmoc-Lys(Boc)-OH as the linker to conjugate two FAPI-04 structures by an amide reaction. The resulting product was further modified by DOTA groups to allow for conjugation with radioactive metals. Both [68Ga]Ga-(FAPI-04)2 and [177Lu]Lu-(FAPI-04)2 showed a radiochemical purity of >99% and remained stable in vitro. In vivo, micro-PET images of SKOV3, A431, and H1299 xenografts revealed that the tumor uptake of [68Ga]Ga-(FAPI-04)2 was about twice that of [68Ga]Ga-FAPI-04 and that the accumulation of [68Ga]Ga-(FAPI-04)2 at the tumor site did not significantly decrease even 3h after injection. The tumor-abdomen ratio of [68Ga]Ga-(FAPI-04)2 images was significantly higher than that of [18F]F-FDG images. For radionuclide therapy, [177Lu]Lu-(FAPI-04)2 effectively retarded tumor growth and displayed good tolerance. In conclusion, the DOTA-Suc-Lys-(FAPI-04)2 design enhanced its uptake in FAP-expressing tumors, improved its retention time at the tumor site, and produced high-contrast imaging in xenografts after radionuclide labeling. Furthermore, it showed a noticeable antitumor effect. DOTA-Suc-Lys-(FAPI-04)2 provides a new approach for applying FAPI derivatives in tumor theranostics.
[18F]FAPI-42 PET/CT versus [18F]FDG PET/CT for imaging of recurrent or metastatic gastrointestinal stromal tumors. [2022]Label="PURPOSE">PET has been important for monitoring recurrence and metastasis of Gastrointestinal Stromal Tumors (GISTs) and the selection of therapeutic strategies. A significant portion of GISTs lesions show negative FDG uptake and therefore calls for more tumor-specific imaging biomarkers. This study compared the imaging performance of [18F]FAPI-42 PET/CT and [18F]FDG PET/CT in recurrent or metastatic gastrointestinal stromal tumors (R/M GISTs).
Recent Advances in Cancer Imaging with 64CuCl2 PET/CT. [2023]Copper is required for cancer cell proliferation and tumor angiogenesis. Radioactive copper-64 chloride (64CuCl2) is a useful radiotracer for cancer imaging with position emission tomography (PET) based on increased cellular uptake of copper mediated by human copper transporter 1 (hCtr1) expressed on cancer cell membrane. Significant progress has been made in research of using 64CuCl2 as a radiotracer for cancer imaging with PET. Radiation dosimetry study in humans demonstrated radiation safety of 64CuCl2. Recently, 64CuCl2 was successfully used for PET imaging of prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Based on the findings from the preclinical research studies, 64CuCl2 PET/CT also holds potential for diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and detection of intracranial metastasis of copper-avid tumors based on low physiological background of radioactive copper uptake in the brain. Copper-64 radionuclide emits both β+ and β- particles, suggesting therapeutic potential of 64CuCl2 for radionuclide cancer therapy of copper-avid tumors. Recent progress in production of therapeutic copper-67 radionuclide invites clinical research in use of theranostic pair of 64CuCl2 and 67CuCl2 for cancer imaging and radionuclide therapy.
The emerging value of 64Cu for molecular imaging and therapy. [2021]Along with other novel metallic radionuclides, copper-64 (64Cu) is currently being investigated as an alternative option to the gallium-68 (68Ga) and lutetium-177 (177Lu) radiopharmaceuticals widely used for targeting somatostatin receptors, expressed by neuroendocrine tumors (NETs), and recently prostate specific membrane antigen (PSMA), expressed by prostate cancer cells. This interest is mostly driven by the peculiar nuclear properties of 64Cu that make it an almost ideal example of theranostic radionuclide. In fact, 64Cu emits both low-energy positrons, β- particles and a swarm of Auger electrons. This combination of different emissions may allow to collect high-resolution PET images, but also to use the same radiopharmaceutical for eliciting a therapeutic effect. Another unique behavior of 64Cu originates from the fundamental biological role played in organisms by the ionic forms of the copper element, which is naturally involved in a multitude of cellular processes including cell replication. These intrinsic biological characteristics has led to the discovery that 64Cu, under its simplest dicationic form Cu2+, is able to specifically target a variety of cancerous cells and to detect the onset of a metastatic process in its initial stage. This short review reports an outline of the status of 64Cu radiopharmaceuticals and of the most relevant results that are constantly disclosed by preclinical and investigational clinical studies.
Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent. [2023]Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (64Cu), a form of copper chloride (64CuCl2), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 (68Ga) as a radionuclide precursor for labelling radiopharmaceuticals used to investigate neuroendocrine tumors and prostate cancer. This emerging interest is also related to the nuclear properties of 64CuCl2 that make it an ideal theragnostic nuclide. Indeed, 64CuCl2 emits β+ and β- particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of 64CuCl2 for the radionuclide cancer therapy of copper-avid tumors. Recently, 64CuCl2 was successfully used to image prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Copper cancer uptake was related to the expression of human copper transport 1 (hCTR1) on the cancer cell surface. Biodistribution, toxicology and radiation safety studies showed its radiation and toxicology safety. Based on the findings from the preclinical research studies, 64CuCl2 PET/CT also holds potential for the diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and the detection of the intracranial metastasis of copper-avid tumors based on the low physiological background of radioactive copper uptake in the brain.
Copper-64-labeled antibodies for PET imaging. [2016]In the imaging of tumors using radiolabeled monoclonal antibodies, the use of PET gives increased sensitivity over conventional gamma camera imaging techniques. Copper-64, a positron-emitting radionuclide, has been labeled to 1A3, an anticolorectal carcinoma monoclonal antibody, and its fragments 1A3-F(ab')2 utilizing the bifunctional chelate Br-benzyl-TETA. The 64Cu-labeled intact 1A3 and 1A3-F(ab')2 have been evaluated as potential imaging agents for PET. Biodistribution studies of 64Cu-benzyl-TETA-1A3 and 64Cu-benzyl-TETA-1A3-F(ab')2 in tumor-bearing hamsters were compared with those of 111In-Br phi HBED-1A3, 111In-Br phi HBED-1A3-F(ab')2 and 125I-labeled intact 1A3 and 1A3-F(ab')2. Tumor uptake of 64Cu-labeled intact 1A3 and fragments in the hamster model was superior to both 111In- and 125I-labeled intact 1A3 and fragments. Human dosimetry data for 64Cu- and 123I-labeled 1A3 and 1A3-F(ab')2 were calculated from biodistribution data in rats. High kidney uptake of 64Cu-benzyl-TETA-1A3-F(ab')2 precludes clinical study at this time; however, the data shows that 64Cu-benzyl-TETA-1A3 would be suitable for positron tomography imaging of colorectal cancer in patients.
Copper-64 radiopharmaceuticals for PET imaging of cancer: advances in preclinical and clinical research. [2023]Copper-64 (T(1/2) = 12.7 hours; beta(+), 0.653 MeV [17.8 %]; beta(-), 0.579 MeV [38.4 %]) has decay characteristics that allow for positron emission tomography (PET) imaging and targeted radiotherapy of cancer. The well-established coordination chemistry of copper allows for its reaction with a wide variety of chelator systems that can potentially be linked to peptides and other biologically relevant small molecules, antibodies, proteins, and nanoparticles. The 12.7-hours half-life of 64Cu provides the flexibility to image both smaller molecules and larger, slower clearing proteins and nanoparticles. In a practical sense, the radionuclide or the 64Cu-radiopharmaceuticals can be easily shipped for PET imaging studies at sites remote to the production facility. Due to the versatility of 64Cu, there has been an abundance of novel research in this area over the past 20 years, primarily in the area of PET imaging, but also for the targeted radiotherapy of cancer. The biologic activity of the hypoxia imaging agent, 60/64Cu-ATSM, has been described in great detail in animal models and in clinical PET studies. An investigational new drug application for 64Cu-ATSM was recently approved by the U.S. Food and Drug Administration (FDA) in the United States, paving the way for a multicenter trial to validate the utility of this agent, with the hopeful result being FDA approval for routine clinical use. This article discusses state-of-the-art cancer imaging with 64Cu radiopharmaceuticals, including 64Cu-ATSM for imaging hypoxia, 64Cu-labeled peptides for tumor-receptor targeting, (64)Cu-labeled monoclonal antibodies for targeting tumor antigens, and 64Cu-labeled nanoparticles for cancer targeting. The emphasis of this article will be on the new scientific discoveries involving (64)Cu radiopharmaceuticals, as well as the translation of these into human studies.