dacarbazine

Few clinical studies investigated the putative link between the activation of immunogenic cell death (ICD) and the oncological outcome. Recent data, published in a Phase 1b trial, demonstrated that an ICD-associated surge in the plasma concentration of high-mobility group box 1 (HMGB1) indicates favorable prognosis in patients with advanced leiomyosarcomas treated with the combination of doxorubicin, dacarbazine and nivolumab.

P2, N=50, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2027

This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported.

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

P2/3, N=135, Not yet recruiting, Linnaeus Therapeutics, Inc. | Phase classification: P3 --> P2/3

In the absence of any prospective comparative study and to evaluate in a real-world context the clinical benefit of re-administering a PD-1 inhibitor (pembrolizumab 200 mg i.v. every 3 weeks, Q3W) with a multi-kinase inhibitor (lenvatinib, but at a reduced dose 10 mg p.o. daily due to its known toxicity) in this frail population of unmet need, we conducted here a retrospective comparison of LEAP-004-proposed combination with CC (carboplatin 4 AUC and dacarbazine 850 mg/m2 i.v. Q3W) in melanoma patients who relapsed to both checkpoint inhibitors, either in combinatorial or in sequential setting, between July 2022 and January 2024. Grade 3-5 treatment-related adverse events were documented in 48.7% (pembrolizumab/lenvatinib) and 75.6% (CC) of patients (p=0.034), which led to treatment discontinuation in 10.3% and 17.8% of cases, respectively. This is the first comparative study in patients with metastatic melanoma refractory to PD-1/CTLA-4 inhibition and showed significantly longer outcomes in cases treated with pembrolizumab/lenvatinib versus CC.

These results, along with the synergic effect with dacarbazine, indicated that PAR may have the potential to be a therapeutic drug for melanoma by triggering apoptosis and suppressing invasion and migration.

MiR-204-5p overexpression with Dacarbazine application resulted in increased the weight, and volume of primary tumors and diminished the proportion of β-Galactosidase expression in melanoma B16-bearing mice. Taking together, our study revealed that although miR-204-5p showed antiproliferative capacities in vitro, it's mimic in combination with Dacarbazine is able to potentiate tumor growth triggering probably a switch from senescent to proliferative phenotype of malignant cells.

P2, N=255, Terminated, Seagen Inc. | Trial completion date: Jun 2026 --> Aug 2024 | Active, not recruiting --> Terminated; The study was prematurely discontinued as the sponsor believes the data collected is enough to show the safety and efficacy of the combinations studied in all cohorts. The decision was not based on any safety and/or efficacy concerns.

P3, N=300, Recruiting, State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia | Trial primary completion date: Dec 2023 --> Dec 2026

Compared to the FDA-approved anti-melanoma agent dacarbazine, NCGC00244536 exhibited more pronounced cytotoxic and antiproliferative effects in melanoma cells. Importantly, NCGC00244536 demonstrated minimal cytotoxicity to low Kdm4b-expressing mouse embryonic fibroblasts. In conclusion, our findings suggest that KDM4B inhibition can override the antitumor effect of p53, and potentially serve as a therapeutic strategy for melanoma.

P3, N=135, Not yet recruiting, Linnaeus Therapeutics, Inc.

This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.

P3, N=256, Completed, Shanghai Junshi Bioscience Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Nov 2023

P4, N=30, Not yet recruiting, First Affiliated Hospital of Zhengzhou University; First Affiliated Hospital of Zhengzhou University

When different combinations of phytochemicals and Dacarbazine were used, the GT plus Dacarbazine treatment group was found to have a 3.5-fold reduction in tumor diameter compared to the Dacarbazine group. The tumor diameters in the Dacarbazine, AP plus GT, GT plus Dacarbazine, and AP plus Dacarbazine treatment groups were 21.4 ± 1.1, 7.6 ± 2.2, 8.6 ± 0.5, and 6.2 ± 1.9 mm, respectively.

Rapidly developed chemoresistance to dacarbazine (DTIC) is a major obstacle in the clinical management of melanoma; however, the roles and mechanisms of epi-transcriptomic RNA modification in this process have not been investigated...Finally, pharmacological inhibition of NAT10 with Remodelin sensitized melanoma cells to DTIC treatment in vitro and in a mouse xenograft model. Our study elucidates the previously unrecognized role of NAT10-mediated ac4C modification in the chemoresistance of melanoma and provides a rationale for developing new strategies to overcome chemoresistance in melanoma patients.

P1/2, N=82, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P2/3, N=96, Not yet recruiting, Children's Cancer Group, China

P1/2, N=197, Completed, Grupo Espanol de Investigacion en Sarcomas | Recruiting --> Completed | Trial completion date: Jun 2025 --> Jun 2024 | Trial primary completion date: Jun 2025 --> Jun 2024

Despite being a rare event, CHL may first develop in extranodal sites, such as the palatine tonsil. In this context, the role of the dentist is pivotal for early diagnosis of the disease. Investigations into the development of primary tonsillar CHL in the oropharynx are needed because the disease has a different clinical course than nodal lesions.

P2, N=46, Active, not recruiting, Academic and Community Cancer Research United | Trial completion date: May 2024 --> Sep 2024

P2, N=110, Completed, University of Cologne | Active, not recruiting --> Completed

He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2 cm × 1 cm. We discuss this rare case and review related literature.

P2, N=30, Recruiting, Shandong First Medical University Affiliated Cancer Hospital; Shandong First Medical University Affiliated Cancer Hospital

P3, N=500, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: May 2024 --> Sep 2024

P3, N=165, Recruiting, Shanghai Kechow Pharma, Inc. | Not yet recruiting --> Recruiting

P2, N=146, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P3, N=1500, Active, not recruiting, University of Cologne | Recruiting --> Active, not recruiting

P3, N=1202, Completed, University College, London | Active, not recruiting --> Completed | Trial completion date: May 2023 --> May 2024

P3, N=470, Recruiting, Erasca, Inc. | Not yet recruiting --> Recruiting

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024

P2, N=71, Recruiting, Memorial Sloan Kettering Cancer Center

P3, N=995, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2032 --> Apr 2025 | Trial primary completion date: Jun 2023 --> Mar 2024

P2, N=98, Recruiting, Philogen S.p.A. | Trial primary completion date: Dec 2023 --> Dec 2024

P3, N=470, Not yet recruiting, Erasca, Inc.

We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity of drugs including a classic chemotherapeutic-dacarbazine-and an antiangiogenic VEGFRs inhibitor-cediranib. In this study, we explored the response of A375 and RPMI7951 melanoma lines to CPL304110 (CPL110), a novel selective inhibitor of fibroblast growth factor receptors (FGFRs), and compared its efficacy with that of AZD4547, the first-generation FGFRs selective inhibitor...Interestingly, 1,25(OH)2D3 and CPL304110 co-treatment resulted in activation of the ERK1/2 pathway in A375 cells. Our results strongly suggested possible crosstalk between vitamin D-activated pathways and activity of FGFR inhibitors, which should be considered in further clinical studies.

P1, N=41, Completed, PTC Therapeutics | Active, not recruiting --> Completed

P2, N=146, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jun 2026 --> May 2024

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

P3, N=325, Active, not recruiting, Advenchen Laboratories, LLC | Trial completion date: Apr 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

Finally, this study underscores the potential therapeutic significance of cabotegravir in melanoma treatment. The findings also raise the prospect of using antiretroviral drugs to downregulate PD-L1 expression, potentially enhancing the therapeutic responses of immune checkpoint inhibitors.