Targeted Radionuclide Therapy for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of California, Davis
Disqualifiers: Congestive heart failure, Active infection, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a Phase I study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostics pair in patients with metastatic non small cell lung cancer (NSCLC).
Do I need to stop my current medications for the trial?
The trial requires that you stop any prior systemic therapy at least 2 weeks before the PET scan, which is a washout period (time without taking certain medications).
What data supports the effectiveness of the treatment [177Lu]Lu DOTA-ABM-5G for non-small cell lung cancer?
Research on similar treatments using Lutetium-177, like [177Lu]Lu-PSMA-617 for prostate cancer and 177Lu-DOTA-TATE for neuroendocrine tumors, shows that Lutetium-177 can effectively target and treat tumors by delivering radiation directly to cancer cells, leading to tumor uptake and potential remission without significant side effects.
12345Is there any safety data available for targeted radionuclide therapy using Lutetium-177 in humans?
The study on [177Lu]Lu-DOTA-ZOL for bone pain relief in patients with cancer that has spread to the bones provides some safety data, indicating it has been evaluated for safety in humans.
13456What makes the drug [177Lu]Lu DOTA-ABM-5G, [68Ga]Ga DOTA-5G unique for treating non-small cell lung cancer?
This drug is unique because it combines diagnostic and therapeutic capabilities by using two different isotopes: gallium-68 for imaging and lutetium-177 for targeted radionuclide therapy, allowing for precise targeting and treatment of cancer cells.
12578Eligibility Criteria
This trial is for patients with advanced non-small cell lung cancer that has spread to other parts of the body. Participants should be adults who have tried previous treatments without success and are now looking for new options.Inclusion Criteria
I have available tumor tissue samples from previous tests.
I can take care of myself but might not be able to do heavy physical work.
My lung cancer has spread and can be measured by scans.
+10 more
Exclusion Criteria
INR >2.0: PTT>15 seconds above ULN
Pregnant or lactating women
Psychiatric illness/social situations that would interfere with compliance with study requirements
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Imaging and Stratification
Participants undergo [68Ga]Ga DOTA-5G PET/CT scans to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy
2 hours
1 visit (in-person)
Treatment
Participants receive a single dose of [177Lu]Lu DOTA-ABM-5G therapy
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
60 days
2 visits (in-person)
Participant Groups
The study is testing two related drugs, [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G, to see if they're safe and effective in treating metastatic lung cancer. It's an early-phase trial, meaning it's one of the first times these drugs are being given to people.
1Treatment groups
Experimental Treatment
Group I: [177Lu]Lu DOTA-ABM-5G single dose therapy studyExperimental Treatment1 Intervention
Patients will be undergo \[68Ga\]Ga DOTA-5G PET/CT scans to confirm eligibility for the \[177Lu\]Lu DOTA-ABM-5G therapy. Patients with sufficient lesion uptake of \[68Ga\]Ga DOTA-5G PET/CT will be offered therapy.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of California Davis Comprehensive Cancer CenterSacramento, CA
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Who Is Running the Clinical Trial?
University of California, DavisLead Sponsor
United States Department of DefenseCollaborator
References
New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). [2022]Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis and radionuclide therapy of prostate cancer. This study reports conversion of a previously reported 68Ga-imaging agent, [68Ga]Ga-P16-093, to a Lu-177 radionuclide therapeutic agent. Substitution of the HBED-CC metal chelating group with DOTA(GA)2 led to P17-087 (4) and P17-088 (7). Both agents showed excellent PSMA binding affinity (IC50 = 10-30 nM) comparable to that of recently FDA-approved [177Lu]Lu-PSMA-617 (Pluvicto). Biodistribution studies in PSMA expressing tumor bearing mice showed that [177Lu]Lu-4 exhibited very high tumor uptake and a fast blood clearance similar to those of [177Lu]Lu-PSMA-617. Conversely, [177Lu]Lu-7, containing an albumin binder, extended its blood half-life and exhibited significantly higher uptake and longer tumor residence time than [177Lu]Lu-4 and [177Lu]Lu-PSMA-617. The switch from chelator HBED-CC to DOTA(GA)2 and the switch from the imaging isotope gallium-68 to the therapeutic isotope lutetium-177 have successfully transformed a PSMA-targeting agent from diagnosis to promising radionuclide therapeutic agents.
¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. [2019]Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing countries.
Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. [2023]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study, we tried to evaluate the efficiency of Luthetium-177 (177Lu) radiolabeled DOTA-Peptide 2 (177Lu-DOTA-Peptide 2) as a new radioantagonist in HT-29 human colorectal cancer in vitro and in vivo.
[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results. [2020]Label="BACKGROUND" NlmCategory="BACKGROUND">[177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers.
Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023]Label="Background" NlmCategory="UNASSIGNED">Lutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored.
Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). [2023]Lutetium-177 (Lu-177) prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a promising therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is limited data of its efficacy and safety in Asian population. We aim to explore the clinical outcomes of Lu-177 PSMA-RLT in this population.
An estradiol-conjugate for radiolabelling with 177Lu: an attempt to prepare a radiotherapeutic agent. [2013]177Lu is presently being considered as one of the most promising radionuclide for targeted therapy owing to its suitable decay characteristics. 177Lu in high radionuclidic purity (99.99%) and moderate specific activity (100-110 TBq/g) was produced using enriched (60.6% 176Lu) Lu2O3 target. The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is known to form stable complexes with lanthanides. Herein, we describe a novel attempt to introduce 177Lu in the estradiol moiety through a steroidal-BFCA (Bifunctional Chelating Agent) conjugate. The preparation of a steroid conjugate via coupling of 6alpha-amino-17beta-estradiol with a C-functionalized DOTA derivative viz. p-NCS-benzyl-DOTA as a BFCA and thereafter the radiolabelling of the conjugate with 177Lu is reported. Biological activity of the resultant estradiol-DOTA conjugate after radiolabelling was studied by carrying out preliminary in vitro cell uptake studies with MCF-7, human breast carcinoma cell line expressing estrogen receptors as well as binding studies with anti-estradiol antibodies.
In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. [2020]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as "No Carrier Added" (NCA) 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA-(Tyr3)-octreotate with NCA 177Lu ("NCA-LuTATE") and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB) and quantitative 3D SPECT (qSPECT) 177Lu imaging.