Radioactive Drugs for Breast Cancer
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Novartis Pharmaceuticals
Disqualifiers: Low blood counts, QTcF ≥ 470 msec, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-NNS309 and the safety and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer (BC), triple negative breast cancer (TNBC) and colorectal cancer (CRC).
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug [177Lu]Lu-NNS309 for breast cancer?
Research on similar drugs, like trastuzumab labeled with 177Lu, shows increased effectiveness in breast cancer cells, suggesting that [177Lu]Lu-NNS309 might also be effective. Additionally, 177Lu has been used successfully in other cancer treatments, indicating its potential as a powerful cancer-fighting agent.
12345Is the treatment with radioactive drugs like [177Lu]Lu-NNS309 generally safe for humans?
Research on similar radioactive drugs, like 177Lu-DOTATATE, shows they are generally considered safe, with studies focusing on their effects on organs and blood. However, they can cause some kidney and blood-related side effects, which are monitored during treatment.
12367What makes the drug [177Lu]Lu-NNS309 unique for treating breast cancer?
The drug [177Lu]Lu-NNS309 is unique because it uses a radioactive isotope, Lutetium-177, which emits beta particles to target and destroy cancer cells, potentially offering a more direct and potent treatment compared to traditional therapies. This approach is similar to other 177Lu-based treatments that have shown effectiveness in targeting specific cancer cells, such as HER2-positive breast cancer, by combining the radioactive element with antibodies that specifically bind to cancer cell markers.
238910Eligibility Criteria
This trial is for adults with certain advanced cancers (pancreatic, lung, breast, colorectal) that can't be removed by surgery or have spread. They should have tried other treatments unless they couldn't due to health reasons. Their cancer must also show up on a special scan using [68Ga]Ga-NNS309.Inclusion Criteria
I am 18 years old or older.
My breast cancer is advanced, cannot be surgically removed, and has worsened after at least 2 treatments.
I have advanced pancreatic cancer and have had chemotherapy, unless I was unable to receive it.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging
Patients are initially imaged with a [68Ga]Ga-NNS309 PET/CT or PET/MRI scan to evaluate eligibility for [177Lu]Lu-NNS309 treatment
Up to 3 days
1 visit (in-person)
Dose Escalation
Different doses of [177Lu]Lu-NNS309 are tested to identify recommended dose(s) for further evaluation
Up to 24 weeks
Dose Expansion
Safety and preliminary efficacy of [177Lu]Lu-NNS309 at the recommended dose(s) are examined
Up to 24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
36 months
Participant Groups
[177Lu]Lu-NNS309 and [68Ga]Ga-NNS309 are being tested for safety and effectiveness in treating specific advanced cancers. The study will look at how the body processes these substances and whether they help in detecting or fighting cancer.
1Treatment groups
Experimental Treatment
Group I: Arm 1Experimental Treatment2 Interventions
Patients will receive \[68Ga\]Ga-NNS309, and if eligible, \[177Lu\]Lu-NNS309
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BAMF HealthGrand Rapids, MI
Novartis Investigative SiteMontreal, Canada
Stanford University Medical CenterStanford, CA
Massachusetts General HospitalBoston, MA
Loading ...
Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of 177Lu-PSMA-EB-01 (denoted as [177Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC).
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.
Toxicity of trastuzumab labeled 177Lu on MCF7 and SKBr3 cell lines. [2015]In this study, we labeled trastuzumab with (177)Lu to synthesize a new radiopharmaceutical for therapy of breast cancer and at the first stage investigated its therapeutic effects on SKBr3 and MCF7 breast cancer cell lines. Trastuzumab-(177)Lu showed very good in-vitro characteristics such as high radiochemical purity (91+/-0.9%), good stability in PBS buffer (86+/-2.3%) and blood serum (81+/-2.7%) up to 96 h, appropriate immunoreactivity (85.4+/-1.1%) and high cytotoxicity in HER2 expression cells. 5 fold increase in toxicity of trastuzumab-(177)Lu was observed when compared with unlabeled trastuzumab on SKBr3 cells.
Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]Label="PURPOSE OF REVIEW">[177Lu]Lu-PSMA-617 is a radiopharmaceutical that emits beta-minus radiation and targets prostate-specific membrane antigen (PSMA)-positive prostate cancer. Despite its clinical success, there are still patients not showing sufficient response rates. This review compiles latest studies aiming at therapy improvement in [177Lu]Lu-PSMA-617-naïve and -resistant patients by alternative or combination treatments.
In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. [2019]Label="OBJECTIVE" NlmCategory="OBJECTIVE">Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy.
Long-term outcome of indigenous 177Lu-DOTATATE PRRT in patients with Metastatic Advanced Neuroendocrine Tumours: a single institutional observation in a large tertiary care setting. [2022]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting.
Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. [2018]Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is regarded as a safe treatment option with promising results for patients with neuroendocrine neoplasia (NEN). We aimed to study the absorbed organ and tumor doses, the renal and hematological toxicity as well as their mutual interaction. Another aim was the identification of adverse effects as possible predictors which may affect survival.
Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate. [2013]177Lutetium (177Lu) is a member of the family of elements known as lanthanides or rare earths. Monoclonal antibody (MAb) CC49, a murine IgG1, which is reactive with the tumor-associated antigen, TAG-72, has been shown previously to react with a wide range of human carcinomas; CC49 reacts to a different epitope on the TAG-72 molecule than MAb B72.3 and has a higher binding affinity. We report here the first use of a 177Lu-labeled immunoconjugate, 177Lu-CC49, in an experimental therapy model for human carcinoma. 177Lu-CC49 was shown to delay the growth of established LS-174T human colon carcinomas in athymic mice at a single dose of 50 microCi. Overt toxicity was observed with the administration of approximately 500 microCi of 177Lu-CC49 in which 5 of 9 mice died of apparent marrow toxicity. A single administration of 200 or 350 microCi of 177Lu-CC49, however, was shown to eliminate established tumors through the 77-day observation period after MAb administration. Dose fractionation experiments revealed that at least 750 microCi of 177Lu-CC49 (250 microCi/week for 3 consecutive weeks) was well tolerated in that 9 of 10 mice survived. Moreover, this dose schedule was able to eliminate the growth of relatively large (300 mm3) human colon tumor xenografts in 90% of the animals treated. Single-dose and dose fractionation studies were also carried out with an isotype-matched control MAb, 177Lu-MOPC-21. In all dose schedules, a large differential was seen between the therapeutic effects of the 177Lu-CC49 versus that of the 177Lu-control MAb. The merits and limitations of the use of 177Lu-labeled immunoconjugates (in particular, 177Lu-CC49) are discussed in terms of potential novel therapeutics for human carcinoma.
Dose-dependent cell cycle arrest and apoptosis in HER2 breast cancer cells by177Lu-CHX-A"-DTPA-Trastuzumab. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Trastuzumab is a Food and Drug Administration-approved humanized monoclonal antibody which targets the extracellular domain of human epidermal growth factor receptor 2 (HER2) receptor overexpressed on HER2-positive breast cancer cells. The combination of Lutetium-177 (177 Lu) (t½= 6.7 days, Eβmax497 keV (78.6%) and trastuzumab makes it a suitable targeting agent for radioimmunotherapy. In preclinical and clinical studies,177 Lu-Trastuzumab has proven to be effective for the treatment of HER2-positive malignancies such as breast and ovarian cancer.
Comparative studies on the potential use of 177Lu-based radiopharmaceuticals for the palliative therapy of bone metastases. [2020]Purpose: In recent years, radionuclides like 177Lu have been considered promising material for the creation of therapeutic radiopharmaceuticals. With the therapeutic use of radiopharmaceuticals, the absorbed doses per tumor may exceed 10 Gy. It is extremely important that doses absorbed by healthy organs and tissues do not exceed the threshold for the incidence of deterministic effects.Materials and methods: The potential use of the radionuclide lutetium-177 for the palliative treatment of pain in bone metastases is analyzed. The radionuclide 177Lu is a beta-emitting nuclide with a maximal energy of 0.49 MeV and a half-life of 6.6 days (161 h). Two therapeutic agents were considered: methylene diphosphonate (MDP) and ethylenediamine tetramethylene phosphonic acid (EDTMP). Both drugs contain phosphorus compounds in their composition, which ensures high tropism in bone tissue. For both drugs, biokinetic models of 177Lu's behavior in the human body are created. A number of studies have shown that the radiochemical stability of these drugs is about 99%: these calculations took into account the presence of a free 177Lu radionuclide in each solution. The absorbed doses in organs and tissues when using the radiopharmaceuticals 177Lu-MDP and 177Lu-EDTMP, as well as the currently used drugs 153Sm-EDTMP and 89SrCl2, are compared. In order to assess the risk of the patient's exposure to a radiopharmaceutical, the absorbed doses are calculated for each organ where the radioactive label is mainly deposited: the kidneys, red bone marrow, liver and bone surface.Results: The intensity of dose accumulation when using different drugs on the pathological focus is different. The drug 177Lu-MDP is faster than other drugs when it comes to the full realization of the expected dose; therefore, a therapeutic effect is achieved faster when it is used. The slowest absorbed dose accumulates when strontium chloride is used. To compare the effectiveness of preparations based on the 177Lu radionuclide, an analysis of the radiopharmaceuticals currently used for the palliative therapy of bone metastases (89SrCl2 and 153Sm-EDTMP) was performed. For 89Sr, the most vulnerable organs are the kidneys, red bone marrow and liver, while for 153Sm-EDTMP, red marrow bone is most vulnerable. For radiopharmaceuticals based on the 177Lu radionuclide, the most vulnerable organs are the kidneys, liver and red bone marrow. This proves the effectiveness of the 177Lu-MDP and 177Lu-EDTMP radiopharmaceuticals.Conclusions: According to the results of the calculations, 177Lu-EDTMP and 177Lu-MDP demonstrate the best results for the palliative therapy of bone metastases.