Recentin (cediranib)

P3, N=579, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2025

Cediranib (20 mg) plus etoposide and cisplatin is well tolerated and has promising clinical activity.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2025

Cediranib and thalidomide effectively reduced tumor size over time. The accessibility of Evans Blue outside the tumor core continuously decreased over time. The vascular density was significantly decreased after treatment while the proportion of normal vessels remained unchanged over time. In contrast to histological studies, DCE-MRI did not tackle any significant change in hemodynamic parameters, in the core or margins of the tumor, whatever the parameter used or the pharmacokinetic model used. While cediranib and thalidomide were effective in decreasing the tumor size, they were ineffective in transiently increasing the delivery of agents in the core and the margins of the tumor.

P2, N=120, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jun 2025

Eight randomized controlled trials (RCTs) were included in the systematic review comprising 3,021 patients evaluated efficacy and safety of PARP inhibitors: Olaparib, niraparib and veliparib with combinations of bevacizumab, carboplatin, cisplatin, cediranib, cyclophosphamide and paclitaxel. Niraparib and veliparib were notably associated with grade 3 or higher anaemia, neutropenia, and thrombocytopenia, olaparib caused fatigue and gastrointestinal disturbances while bevacizumab and cediranib caused hypertension. This review suggested combined PARP inhibitor and chemotherapy significantly prolonged progression-free survival especially in patients with BRCA mutation compared to chemotherapy and the combined therapy is safe.

P2/3, N=587, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Jun 2025

In patients with pMMR-CRC or PDAC, durvalumab + olaparib and durvalumab + cediranib showed limited antitumor activity. Different immune components of the TME were associated with treatment outcomes.

PARPi-based therapy showed considerable efficacy for mCRPC patients with HRD in 2nd -line setting. However, patients should be treated accordingly based on their genetic background as well as the efficacy and safety of the selected regimen.

Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

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