Recentin (cediranib)

P2, N=122, Active, not recruiting, National Cancer Institute (NCI) | Terminated --> Active, not recruiting | Trial completion date: Jun 2022 --> Apr 2025

P2, N=288, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Dec 2024 | Trial primary completion date: Apr 2024 --> Dec 2024

P1/2, N=117, Active, not recruiting, National Cancer Institute (NCI)

Then, using the drug repurposing method with the Connectivity Map CLUE Query tools, potential drugs such as Forskolin, Gestrinone, Cediranib, Apicidine, and Everolimus, which showed a highly negative correlation with the expression levels of the selected genes, were identified. This study provides a method to develop new approaches to diagnosing and treating gastric cancer by comparing the transcriptome profiles of patients gastric cancer and performing a feature engineering-assisted drug repurposing analysis based on cancer data.

P2, N=122, Terminated, National Cancer Institute (NCI) | Active, not recruiting --> Terminated; Inadequate accrual rate

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.

P2, N=90, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2025

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024

P1, N=19, Active, not recruiting, National Cancer Institute (NCI)

P1/2, N=155, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Jan 2025

These findings provide a preclinical framework supporting the potential of dual targeting HER2 and VEGFR as a promising therapeutic strategy to improve outcomes in patients with OC.

Here, we demonstrated that anti-angiogenic agents, bevacizumab and cediranib, increased the sensitivity of olaparib in HRP EOC cells by suppressing HR activity. In addition, CRY1 inhibition also sensitized EOC cells to olaparib. These data suggested that anti-angiogenic agents and CRY1 inhibitors will be the promising candidate in the combination therapy with PARP inhibitors in HR-proficient EOC.

P1/2, N=384, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jan 2024 --> Dec 2024

In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8 T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy.

P2, N=139, Completed, University of Oxford | Active, not recruiting --> Completed

OCTOVA demonstrated the activity of O + C in women with recurrent disease, offering a potential non-chemotherapy option.

P1, N=64, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024

P2, N=149, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2023

P1/2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

Bortezomib and Axitinib exhibited high efficacy on the patient's sample...Other FGFR inhibitors, including Olverematinib, AZD4547, Axitinib, Cediranib, Dovitinib, and Lenvatinib, also demonstrated exquisite sensitivity. Despite extensive screening, no other single agents or drug combinations exhibited increased effectiveness in the ZMYM2: : FGFR1 transformed BaF3 cells except for Trametinib, a MEK inhibitor, and the combination of Belvarafenib (RAF inhibitor) and Gilteritinib (FLT3 inhibitor)... Ex vivo drug sensitivity assays demonstrated the highly selective efficacy of FGFR inhibitors in ZMYM2: : FGFR1 fusion-positive leukemia cells and a fusion-expressing BaF3 cell line. Mutations in the FGFR1 kinase domain (ZMYM2: : FGFR1 F1171L) could contribute to Ponatinib insensitivity. These ex vivo drug screening results provide further support for ongoing clinical trials which are investigating the use of single agent Pemigatinib and other FGFR1 inhibitors for the treatment of patients with FGFR1-fusion positive leukemias.

Preclinical results and Phase II and III clinical trial data support the mechanistic rationale for the efficacy of these agents in combination. Future investigations should explore the effectiveness of cediranib and other anti-angiogenic agents with a PARP inhibitor to elicit an antitumor response and sensitize cancers to immunotherapy.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Nov 2023

P2, N=164, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2024 --> Dec 2023

P2, N=72, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Aug 2024

P2, N=149, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Nov 2024

Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era.

P3, N=579, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Aug 2024

Approaches utilized for targeted drug delivery to the GBM were also discussed.  This article also describes the recent in vivo, in vitro and ex vivo advances using innovative theranostic approaches.

Durvalumab plus olaparib increased immune cell infiltration of TME with clinical benefit in some LMS patients. Baseline M1-macrophage and B-cell activity may identify LMS patients with favorable outcomes on immunotherapy and should be further evaluated.

Treatments were randomly assigned 1:2:2:2 to SOC (weekly paclitaxel, topotecan or liposomal doxorubicin), DOC, DC or OC. Conclusions None of the experimental arms improved PFS compared with SOC. SOC was active in this heavily pretreated population.

Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

P2/3, N=562, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

P2, N=288, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

This NMA showed that carboplatin + pegylated liposomal doxorubicin + bevacizumab seems to increase the efficacy of standard second-line CT. These strategies can be considered when treating patients with relapsed platinum-sensitive ovarian cancer without BRCA mutations. This study provides systematic comparative evidence for the efficacy of different second-line therapies for relapsed ovarian cancer.

Our data indicate that upregulated MIR4435-2HG expression levels are significantly correlated with a poor prognosis of UCB patients. MIR4435-2HG promotes bladder cancer progression, mediates cell cycle (de)regulation and modulates mTOR signaling. MIR4435-2HG is an oncogenic lncRNA in UCB that may serve as a diagnostic and therapeutic target.

Conclusions Longitudinal testing of cfDNA by TS provides a non-invasive tool for detection of tumour-derived mutations and mechanisms of PARPi resistance that may aid in directing patients to appropriate therapeutic strategies. With cfDNA fragmentation analyses, CHIP was identified in several patients and warrants further investigation.

P2, N=60, Recruiting, CCTU- Cancer Theme | Trial completion date: Apr 2022 --> Nov 2025 | Trial primary completion date: Apr 2022 --> Nov 2025

P1, N=64, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2022 --> Dec 2023

Our earlier studies documented that 1,25(OH)D and its low-calcaemic analogues potentiate the effectiveness of dacarbazine and cediranib, a pan-VEGFR inhibitor...Thus, patient-derived cells were preconditioned with 1,25(OH)D and treated with cediranib or vemurafenib, a BRAF inhibitor, depending on the BRAF mutation status of the patients enrolled in the study...Interestingly, regardless of the strict selection, cancer-derived fibroblasts (CAFs) became the major fraction of cultured cells over time, suggesting that melanoma growth is dependent on CAFs. In conclusion, the results of our study strongly emphasise that the active form of vitamin D, 1,25(OH)D, might be considered as an adjuvant agent in the treatment of malignant melanoma.

P2, N=164, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P2, N=72, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jun 2023 --> Jul 2022

We established patient-derived tumor organoids (PDTOs) from mCRC biopsies and, based on favorable physicochemical and pharmacokinetic properties, selected 3 TKIs (sunitinib, cediranib and osimertinib). While this is likely due to high intra-tumoroid concentrations reached by osimertinib—the mechanism of action at these concentrations remains unknown and is subject to further studies. In parallel, we propose that a HDSE osimertinib regimen warrants clinical exploration as a potential new treatment option for mCRC.