Delving into the Latest Updates on Cediranib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cediranib (USAN/INN), Cediranib-maleate, Recentin

+ [4]

Target

VEGFR1 x VEGFR2 x VEGFR3

Mechanism

VEGFR1 antagonists(Vascular endothelial growth factor receptor 1 antagonists), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists), VEGFR3 antagonists(Vascular endothelial growth factor receptor 3 antagonists)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [5]

Active Indication

Endometrioid carcinoma ovaryFallopian Tube Clear Cell AdenocarcinomaOvarian clear cell adenocarcinoma+ [62]

Inactive Indication

acute leukemiaAcute Lymphoblastic LeukemiaAcute myeloid leukaemia with 11q23 abnormality+ [118]

Originator Organization

AstraZeneca PLC

Active Organization

AstraZeneca PLC

National Cancer Institute

Inactive Organization

Wyeth AB

University College London

AstraZeneca Pharmaceuticals Co. Ltd.

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (US), Orphan Drug (EU)

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Structure/Sequence

Molecular FormulaC25H27FN4O3

InChIKeyXXJWYDDUDKYVKI-UHFFFAOYSA-N

CAS Registry288383-20-0

A Randomized Phase II Trial of Triplet Therapy (A PD-L1 Inhibitor Durvalumab (MEDI4736) in Combination With Olaparib and Cediranib) Compared to Olaparib and Cediranib or Durvalumab (MEDI4736) and Cediranib or Standard of Care Chemotherapy in Women With Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Cancer Who Have Received Prior Bevacizumab

This phase II trial studies the possible benefits of treatment with different combinations of the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type of treatment most patients with this condition receive if they are not part of a clinical study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of durvalumab, olaparib and cediranib may work better in increasing the duration of time that the cancer does not progress compared to the usual treatment.

Start Date10 Jun 2021

Sponsor / Collaborator

National Cancer Institute

[+1]

NCT04090567

/ RecruitingPhase 2IIT

Overcoming PARP Inhibitor Resistance in BRCA Germline Mutation Positive Advanced Breast Cancer

This phase II trial studies how well olaparib with cediranib or AZD6738 works in treating patients with germline BRCA mutated breast cancer that has spread to other places in the body (advanced or metastatic). Olaparib, cediranib, and AZD6738 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date28 Jul 2020

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT03741426

/ RecruitingPhase 2IIT

WIndow of Opportunity Clinical Trials Platform for Evaluation of Novel Treatments Strategies in REnal Cell Cancer

Evaluation of proof of mechanism with relation to ktrans and/or CD8 count when 3 different IMPs are given as monotherapy or as combination therapy. These would be administered in the "window of opportunity", prior to nephrectomy in surgically resectable renal cell cancer

Start Date27 Jul 2020

Sponsor / Collaborator

Cambridge University Hospitals NHS Foundation Trust

[+3]

100 Clinical Results associated with Cediranib

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100 Translational Medicine associated with Cediranib

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100 Patents (Medical) associated with Cediranib

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432

Literatures (Medical) associated with Cediranib

01 Jan 2025·Cancer Genomics & Proteomics

Regulation and Function of CCL2 and N-Myc in Retinoic Acid-treated Neuroblastoma Cells

Article

Author: Bruckmueller, Henrike ; Kaehler, Meike ; Schmidt, Berit ; Issa, Reema Sami ; Murra, Nanke ; Waetzig, Vicki ; Pommert, Nina Sophie ; Tim, Vera ; Cascorbi, Ingolf

BACKGROUND/AIM:

Treatment with retinoic acid (RA) often promotes neuroblastoma differentiation and growth inhibition, including the suppression of the expression of the MYCN oncogene. However, RA also targets protumoral chemokines, such as CCL2, which may contribute to the development of resistance. The present study aimed to investigate the regulation and function of CCL2 and N-Myc in RA-treated neuroblastoma cells.

MATERIALS AND METHODS:

In Kelly or SH-SY5Y cells, viability was quantified by cell fitness assays. Expression was analyzed using quantitative PCR and the regulation of proteins using enzyme-linked immunoabsorbent assays (ELISA) or western blots.

RESULTS:

In MYCN-amplified Kelly cells, endogenous CCL2 levels were significantly lower compared to MYCN non-amplified SH-SY5Y cells. Treatment with 5 μM RA increased CCL2 release in both cell lines, but reduced N-Myc levels and cell numbers in Kelly cells. Over-expression of MYCN enhanced viability in SH-SY5Y cells, but did not affect RA-induced CCL2 release, while supplementation of CCL2 in Kelly cells did not prevent RA-mediated growth reduction. Impaired N-Myc or CCL2 signaling reduced the survival of all RA-treated cells and inhibition of N-Myc also decreased CCL2 levels. However, attenuated survival signaling was not generally associated with reduced levels of N-Myc or CCL2. Co-application of RA and the growth factor receptor inhibitors cediranib or crizotinib decreased N-Myc levels only in Kelly cells, while CCL2 release was dependent on the cell type and stimulus.

CONCLUSION:

CCL2 and N-Myc promote the viability of RA-treated cells, although the levels of these mediators were not consistently correlated with cellular outcomes, especially during apoptotic signaling.

20 Dec 2024·JOURNAL OF CLINICAL ONCOLOGY

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005

Article

Author: Kohn, Elise C. ; Brady, Mark F. ; McDonald, Megan E. ; Duska, Linda R. ; Kavecansky, Juraj ; Moore, Richard G. ; Lheureux, Stephanie ; Rose, Peter G. ; McNally, Leah ; Provencher, Michèle ; Street, Daron ; Miller, Austin ; MacKay, Helen ; Wenzel, Lari B. ; Cantuaria, Guilherme ; Kim, Yong-Man ; Bookman, Michael A. ; Lee, Jung-Min ; Powell, Matthew ; Lea, Jayanthi ; Secord, Angeles Alvarez ; Huang, Helen Q. ; Leath, Charles A. ; Cadungog, Mark G.

PURPOSE:

We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC).

PATIENTS AND METHODS:

NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes.

RESULTS:

Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib ( v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, –1.3 to 1.5, P = .8725).

CONCLUSION:

The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

01 Nov 2024·Clinical Lung Cancer

A Phase I Open-Label Study of Cediranib Plus Etoposide and Cisplatin as First-Line Therapy for Patients With Extensive-Stage Small-Cell Lung Cancer or Metastatic Neuroendocrine Non–Small-Cell Lung Cancer

Article

Author: Camidge, D Ross ; Concannon, Kyle F ; Marotti, Marcelo ; Concannon, Kyle F. ; Glisson, Bonnie S. ; Camidge, D. Ross ; Doebele, Robert C. ; Camidge, D.Ross ; Heymach, John V. ; Doebele, Robert C ; Glisson, Bonnie S ; Heymach, John V ; Huang, Chao

INTRODUCTION:

Small cell lung cancer (SCLC) is known to express high levels of the proangiogenic factor vascular endothelial growth factor (VEGF). We assessed the safety and tolerability of cediranib, an oral inhibitor of VEGF receptor tyrosine kinases, in combination with etoposide and cisplatin as first-line therapy for extensive-stage (ES) SCLC or metastatic lung neuroendocrine cancer (NEC).

METHODS:

Patients received up to six 21-day cycles of etoposide (100 mg/m², days 1-3) and cisplatin (80 mg/m², day 1) with once-daily cediranib until disease progression or unacceptable toxicity. Cediranib dosing started at 30 mg with de-escalation cohorts planned based on cycle 1 dose-limiting toxicities (DLTs). An expansion cohort of 12 patients was enrolled at the recommended phase II dose.

RESULTS:

Twenty-two patients (18 with ES SCLC, 4 with NEC) received treatment. Only 4 patients were enrolled at the 30 mg cediranib dose before other studies established 20 mg/day as the recommended dose with chemotherapy. Among the 18 patients enrolled at the 20-mg dose, common adverse events included nausea/vomiting, neutropenia, and diarrhea; 8 patients (44%) had grade 1 or 2 hypertension, and 2 (11%) had grade 3 hemoptysis. For all 18 patients, the objective response rate and median progression-free survival duration were 67% and 7.9 months. Plasma levels of VEGF were significantly higher, and those of soluble VEGFR2 were significantly lower, on day 22 than at baseline but were not correlated with tumor shrinkage.

CONCLUSIONS:

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

100 Deals associated with Cediranib

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External Link

KEGG	Wiki	ATC	Drug Bank
D08881	Cediranib	L01XE32	DB04849

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ovarian Cancer	NDA/BLA	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Ovarian Serous Adenocarcinoma	Phase 3	US	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	JP	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	CA	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	PR	National Cancer Institute	03 May 2016
Ovarian Serous Adenocarcinoma	Phase 3	KR	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	US	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	JP	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	CA	National Cancer Institute	03 May 2016
Platinum-Resistant Primary Peritoneal Carcinoma	Phase 3	PR	National Cancer Institute	03 May 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03314740 (IRFMN-OVA-7289, EudraCT: 2016-003964-38 \| IRFMN-OVA-7289 \| BAROCCO, CTgov)	Phase 2	Recurrent ovarian cancer \| Platinum-Resistant Primary Peritoneal Carcinoma	123	Paclitaxel (Arm A)	vihocprvbz(uniatjxygu) = jzthrkjdvg slbqrmwpxh (oftstmoxaz, xjctobhatr - jvakyganmz) View more	-	10 Jan 2025
				Olaparib+Cediranib (Arm B)	vihocprvbz(uniatjxygu) = igggqftkan slbqrmwpxh (oftstmoxaz, xakksvvjlk - rtfepejxfs) View more
NCT02502266 (NRG-GY005, Pubmed \| J Clin Oncol)	Phase 2/3	Platinum-Resistant Ovarian Carcinoma high-grade serous \| endometrioid	-	Cediranib	yboolnbybg(wyarffewyd) = hzcfsituur sluzdddcoj (hocrgqpjxo ) View more	Negative	20 Dec 2024
				Olaparib	yboolnbybg(wyarffewyd) = vdnqnhafuq sluzdddcoj (hocrgqpjxo ) View more
NCT01391962 (CTgov)	Phase 2	Alveolar Soft Part Sarcoma	34	AZD2171 (Cediranib) (AZD2171 (Cediranib) 30 mg)	tkcyruxcuf(iczcqhzjjn) = gffrsopynm spaeyihkep (rrktvwzwtn, zkpovkvgsp - kfmasifgku) View more	-	19 Sep 2024
				AZD2171 (Cediranib)+Sunitinib Malate (AZD2171 (Cediranib) 30 mg Followed by Sunitinib Malate 37.5 mg)	tkcyruxcuf(iczcqhzjjn) = ugedyzfsbl spaeyihkep (rrktvwzwtn, cxtgjbivhg - zygrhijzvj) View more
407 (ESGO2024)	Phase 2	Recurrent Endometrial Cancer	124	Weekly paclitaxel	adqjvoieeh(vofbqevjpc) = augvmgpgcn zzuhujhpgq (pkvckrfkoc ) View more	-	10 Mar 2024
				Weekly paclitaxel + Cediranib	adqjvoieeh(vofbqevjpc) = hexmhxpjig zzuhujhpgq (pkvckrfkoc ) View more
NCT02974621 (CTgov)	Phase 2	Recurrent Glioblastoma	70	Olaparib+Cediranib (Arm A (Olaparib, Cediranib Maleate))	tbjudawgbu(ukiaelpzuw) = vgaxtjcrpw vpzrsdtszw (gdjiurfkir, fnnqbrdjdw - yfvgkxjddx) View more	-	02 Feb 2024
				Bevacizumab (Arm B (Bevacizumab))	tbjudawgbu(ukiaelpzuw) = qtnwyfskwg vpzrsdtszw (gdjiurfkir, qtfikqgnpr - pievkndgvb) View more
NCT02446600 (NRG-GY004, ESMO2023)	Phase 3	Platinum-Sensitive Primary Peritoneal Carcinoma \| Ovarian Serous Tumor \| Ovarian mixed epithelial carcinoma ... gBRCAm View more	565	cediranib (Standard of care (SOC))	fbevfaboga(otejrkqvta) = ufkmagbfpp pahuuupgsz (noyherurle )	Negative	22 Oct 2023
				Olaparib (O)	fbevfaboga(otejrkqvta) = kcqhokfqxi pahuuupgsz (noyherurle )
NCT03660826 (NRG GY012, ASCO2023) Manual	Phase 2	Advanced Endometrial Carcinoma	97	overall	arzjaqsrue(sgacvtqiym) = zzvgghsxvc pegvdstisw (wbmuwikuxs )	Negative	31 May 2023
				Cediranib or Cediranib + Olaparib (IL-6 > 4 pg/ml)	arzjaqsrue(sgacvtqiym) = tdrlvmmgcf pegvdstisw (wbmuwikuxs ) View more
NCT03660826 (NRG-GY012, ASCO2023)	Phase 2	Metastatic endometrial cancer Maintenance	-	Cediranib PO 30 mg Daily	dxhlysisms(agjxwnxnah) = rvchwdibav uizprdeeaz (lnvjhoxobp )	-	31 May 2023
NCT03851614 (DAPPER, ASCO2023)	Phase 2	Leiomyosarcoma	-	Durvalumab plus Cediranib	pxhpnxyrds(dzypquoblc) = eiwpmhiivi fpvqxktzgy (ldjnlmrfjg, 10.7 - NR) View more	-	31 May 2023
SNO2022	Phase 2	Recurrent Glioblastoma	70	Cediranib/Olaparib	giklmobfsp(rcggitokyu) = rdvzqljqgp yeugikzrcb (vjdrixbsbn ) View more	Negative	14 Nov 2022
				Bevacizumab	giklmobfsp(rcggitokyu) = jwtctllgyq yeugikzrcb (vjdrixbsbn ) View more