zoledronic acid

P=N/A, N=20, Active, not recruiting, University of Calgary | Recruiting --> Active, not recruiting

Due to disease progression, lenvatinib was initiated...Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain... The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course.

In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.

P4, N=101, Completed, National Taiwan University Hospital | Recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jul 2023

P3, N=318, Active, not recruiting, UNICANCER | Trial completion date: Dec 2025 --> Dec 2026

P1/2, N=138, Not yet recruiting, Washington University School of Medicine

P4, N=89, Completed, Centre Hospitalier Universitaire de Nice | Unknown status --> Completed | N=350 --> 89

Following 14-days ex vivo expansion with zoledronic acid and interleukin (IL)-2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions, and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro, and in vivo in leukemia bearing xenogeneic mice...Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced anti-leukemic effects of exercise. These findings provide a mechanistic link between exercise, β2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematological malignancies.

Here, we demonstrated that next-generation immunomodulators called cereblon E3 ligase modulators (CELMoDs), as well as lenalidomide and pomalidomide, expanded Th1-like Vδ2+ γδ T cells from PBMCs in the presence of zoledronic acid (ZA). ZA but not these immunomodulatory drugs upregulated BTN3A1 in monocytes. These results suggest that immunomodulatory drugs and ZA have cooperative roles in expansion of Th1-like Vδ2+ γδ T cells, and provide the important knowledge for clinical application of human Vδ2+ γδ T cells as effector cells.

P4, N=300, Recruiting, Lene Bergendal Solberg | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise-afforded protection against bone metastasis progression.

P=N/A, N=100, Recruiting, University of Colorado, Denver | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=80, Recruiting, AUVA Traumazentrum Vienna Site UKH Meidling | Trial completion date: Jul 2025 --> Dec 2030

ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.

The use of bisphosphonates in the therapeutic strategy for JO should be further explored, as should the role of bone resorption in the pathophysiology of the disease.

ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.

Zoledronic acid combined with chemotherapy can effectively treat bone metastases of NSCLC and improve pain stress and bone metabolic status, which has value that can be promoted and applied in clinical treatment.

P2, N=40, Completed, Oslo University Hospital | Active, not recruiting --> Completed

P2, N=27, Completed, Columbia University | Active, not recruiting --> Completed

Overall, 1 % (95 % CI 0.75-1.15) of patients experienced osteonecrosis of jaw related to zoledronic acid. Compared to the Early Breast Cancer Trialist's Collaborative Group meta-analysis, benefit from adjuvant bisphosphonates is lower in recent trials especially in higher risk patients receiving contemporary chemotherapy. The balance between benefits and risks of adjuvant bisphosphonates should be considered in individual patients.

P=N/A, N=20, Active, not recruiting, Lithuanian University of Health Sciences | Recruiting --> Active, not recruiting

In addition, galectin-3 reduced the effector memory compartment of zoledronate-activated Vδ2 T cells. Therefore, our data suggest that an activation of Vδ1 T-cell proliferation as part of a T-cell-based immunotherapy can be of advantage.

P3, N=1360, Not yet recruiting, Shanghai JMT-Bio Inc.

In this study, we established a protocol for ex vivo expansion of Vγ9Vδ2 T cells from healthy donors' peripheral blood mononuclear cells by culture with zoledronate and addition of IL-2, and IL-15 or IL-18 or neither...We found that in the presence of either IL-15 or IL-18, levels of caspase 3 were significantly reduced. Also, IL-15 and IL-18 stimulated cells contained cytotoxicity against cholangiocarcinoma cells, suggesting that stimulated Vγ9Vδ2 T cells may provide a feasible therapy for cholangiocarcinoma.

P4, N=20, Active, not recruiting, Nami Safai Haeri | Recruiting --> Active, not recruiting

ZA decreased phosphorylated ERK (pERK) levels in resistant cell lines and attenuated HER-2 signaling in tamoxifen- and fulvestrant-resistant cells. Moreover, ZA inhibited the migration and invasion in the resistant cell lines, suggesting an ability to inhibit tumor metastasis. The results indicate that ZA has potential for repurposing as an adjuvant treatment for patients with endocrine-resistant breast cancer.

P2, N=44, Recruiting, University of Nebraska | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027

P1, N=24, Recruiting, Emory University

P1, N=22, Recruiting, University of Wisconsin, Madison

Here, we express an anti-CD19 εTRuC in primary γδ T cells that were expanded using zoledronate (Zol) or concanavalin A. We show that the resulting εTRuC γδ T cells were reprogrammed to better recognize CD19-positive B cell tumors and-in case of the Zol-expanded cells-a CD19-expressing colon adenocarcinoma-derived cell line in vitro...Finally, addition of vitamin C promoted the recovery of larger γδ T cell numbers after lentiviral transduction, as used for the expression of the εTRuC. In conclusion, the generation and use of γδ εTRuC T cells might be a new approach for cancer immunotherapy.

The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.

P4, N=20, Recruiting, Aksaray University | Not yet recruiting --> Recruiting

We tried different electroporation procedures (X001, T007, U014, T023) and cell culture conditions (cultured in medium containing zoledronic acid (ZOL)/ IL2 for 5 days or for 10 days) to select out the optimal procedure to acquire high KO/KI efficiency and high cell proliferation rate...Interestingly, the proportion of memory phenotype (CD62L + ) in CAR-γδ T cells after being stimulated was comparable to that of CAR-γδ T cells without stimulation, indicating the potential of the great anti-tumor activity of CAR-γδ T cells after being stimulated in tumor environment (Figure 1F). Our new method successfully generated CAR-γδ T cells with a CAR expression of 20% and in a high proliferation rate, which was determined to exert effective anti-tumor effects.

Here, we observed that osteoclasts reduced the sensitivity of breast cancer cells to DNA damaging agents, including cisplatin and the PARP inhibitor (PARPi) olaparib. Combination therapy utilizing PARPi and zoledronate, which blocks osteoclast activity and thereby reduces the microenvironmental glutamine supply, generated a synergistic effect in reducing bone metastasis. These results identify a role for glutamine production by bone-resident cells in supporting metastatic cancer cells to overcome oxidative stress and develop resistance to DNA-damaging therapies.

P=N/A, N=287, Enrolling by invitation, University of Edinburgh | Recruiting --> Enrolling by invitation

Small-cell lung cancer (SCLC), which accounts for about 15 % of all lung cancers, progresses more rapidly than other histologic types and is rarely detected at an operable early stage. Furthermore, treatments with antiallergic agents tranilast and zoledronic acid, known EMT inhibitors, significantly mitigated the decreased sensitivity of CLDN1-overexpressing SBC-3 cells to DOX. These results suggest that EMT inhibitors might effectively overcome reduced sensitivity to anticancer drugs in CLDN1-overexpressing SCLC cells.

P4, N=20, Not yet recruiting, Aksaray University

Regarding osteoprotective treatment, patients received: 51% Denosumab + calcium + vitamin D, 28% received calcium + vitamin D, 18% did not receive any osteoprotective treatment, and 3% received Zoledronic acid + calcium + vitamin D. BRE occurred in 11,3%  [JG1] of all patients, one patient (0.8%) who presented spinal cord compression, 4% (5 patients) presented pathological fractures, and 6.5% (8 patients) received analgesic radiotherapy. Patients who received treatment with docetaxel had BRE than patients treated with ARTA (28% vs. 72%). Finally, 86% of patients with skeletal events had an ISUP score greater than or equal to 3, while only 14% had an ISUP score of 1-2.

MIDP, a zoledronic acid derivative, can cause the death of human colorectal cancer cells by increasing the level of intracellular reactive oxygen species (ROS)...This study revealed for the first time a possible mechanism of bisphosphonate-induced increase of ROS in malignant tumor cells. This is helpful for the development of new molecular therapeutic targets and can provide new ideas for the combined therapy of bisphosphonates in tumors.

Therapeutic modalities for alleviation of clinical symptoms associated with bone metastasis include surgical resection, radiation, and bone-targeted therapies, including bisphosphonates (e.g., zoledronic acid; ZA) and a humanized antibody against receptor activator of nuclear factor-κB ligand (denosumab). This combination also decreased the nuclear level of yes-associated protein, a core component of Hippo signaling. In conclusion, the present study offers a novel combination for prevention or treatment of bone metastasis of breast cancer.

Donor GDT collected from the same donor of the allo-HCT were enriched from non-mobilized leukapheresis product by stimulation with zoledronic acid and IL-2 for 7 days followed by alpha beta T cell depletion using the Miltenyi CliniMACS...Early results of this trial are promising, which provides validation for continued testing of adoptive transfer of ex vivo expanded donor GDT. Updated results of this trial will be presented at the annual conference.