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

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [4]

Active Indication

Endometrioid carcinoma ovaryFallopian Tube Clear Cell AdenocarcinomaOvarian clear cell adenocarcinoma+ [61]

Inactive Indication

acute leukemiaAcute Lymphoblastic LeukemiaAcute myeloid leukaemia with 11q23 abnormality+ [116]

Originator Organization

AstraZeneca PLC

Active Organization

National Cancer Institute

AstraZeneca PLC

Inactive Organization

Wyeth AB

AstraZeneca Pharmaceuticals Co. Ltd.

University College London

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (US), Orphan Drug (EU)

Structure

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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411

Literatures (Medical) associated with Cediranib

01 Sep 2024·Clinical Colorectal Cancer

A Phase II, Open-Label, Randomized Trial of Durvalumab With Olaparib or Cediranib in Patients With Mismatch Repair—Proficient Colorectal or Pancreatic Cancer

Article

Author: Han, Ming ; Siu, Lillian L ; Lam, Bernard ; Ayodele, Olubukola ; Hernando-Calvo, Alberto ; Avery, Lisa ; Berman, Hal K ; Pugh, Trevor J ; Bruce, Jeffrey P ; Stayner, Lee-Anne ; Hansen, Aaron R ; Salawu, Abdulazeez ; Wang, Ben X ; Razak, Albiruni R A ; Vila-Casadesús, Maria ; Lungu, Ilinca ; Abbas-Aghababazadeh, Farnoosh ; Vivancos, Ana ; Spreafico, Anna ; Yang, S Y Cindy ; Bedard, Philippe L ; Haibe-Kains, Benjamin ; Sanz-Garcia, Enrique

BACKGROUND:

The use of immunotherapy in mismatch repair proficient colorectal cancer (pMMR-CRC) or pancreatic adenocarcinoma (PDAC) is associated with limited efficacy. DAPPER (NCT03851614) is a phase 2, basket study randomizing patients with pMMR CRC or PDAC to durvalumab with olaparib (durvalumab + olaparib) or durvalumab with cediranib (durvalumab + cediranib).

METHODS:

PDAC or pMMR-CRC patients were randomized to either durvalumab+olaparib (arm A), or durvalumab + cediranib (arm B). Co-primary endpoints included pharmacodynamic immune changes in the tumor microenvironment (TME) and safety. Objective response rate, progression-free survival (PFS) and overall survival (OS) were determined. Paired tumor samples were analyzed by multiplexed immunohistochemistry and RNA-sequencing.

RESULTS:

A total of 31 metastatic pMMR-CRC patients were randomized to arm A (n = 16) or B (n = 15). In 28 evaluable patients, 3 patients had stable disease (SD) (2 patients treated with durvalumab + olaparib and 1 patient treated with durvalumab + cediranib) while 25 had progressive disease (PD). Among patients with PDAC (n = 19), 9 patients were randomized to arm A and 10 patients were randomized to arm B. In 18 evaluable patients, 1 patient had a partial response (unconfirmed) with durvalumab + cediranib, 1 patient had SD with durvalumab + olaparib while 16 had PD. Safety profile was manageable and no grade 4-5 treatment-related adverse events were observed in either arm A or B. No significant changes were observed for CD3+/CD8+ immune infiltration in on-treatment biopsies as compared to baseline for pMMR-CRC and PDAC independent of treatment arms. Increased tumor-infiltrating lymphocytes at baseline, low baseline CD68+ cells and different immune gene expression signatures at baseline were associated with outcomes.

CONCLUSIONS:

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.

01 Aug 2024·GYNECOLOGIC ONCOLOGY

A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib

Article

Author: Armstrong, Deborah K ; Xiong, Niya ; Penson, Richard T ; Barry, William T ; Cristea, Mihaela C ; Wenham, Robert M ; Ivy, S Percy ; Chan, Nancy ; Cheng, Su-Chun ; Matulonis, Ursula A ; Olawaiye, Alexander B ; O'Malley, David M ; Matsuo, Koji ; Lee, Jung-Min ; Shapiro, Geoffrey I ; Swisher, Elizabeth M ; Abbruzzese, James L ; Wahner-Hendrickson, Andrea ; Kohn, Elise C ; Liu, Joyce F ; Polak, Madeline

OBJECTIVE:

Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD).

METHODS:

Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity.

RESULTS:

In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23).

CONCLUSIONS:

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.

01 Jul 2024·INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER

Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial

Article

Author: Hasan, Jurjees ; Casbard, Angela ; Pugh, Julia ; Murphy, Alexander D ; Karanth, Suman ; Adams, Richard ; Morgan, Robert D ; Irving, Alys ; Mahmood, Reem D ; Jayson, Gordon C ; Wheeler, Chelsey ; Zhou, Cong ; Salih, Zena ; Clamp, Andrew R ; Ray, Ruby ; White, Ann ; Roberts, Victoria ; Porter, Catharine ; Arnetoli, Giorgio ; Mitchell, Claire

Objective:

Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction.

Methods:

A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction. Cediranib (20 mg/day) was added to paclitaxel (70 mg/m2/week) within 9 weeks of starting paclitaxel if pretreatment bowel symptoms had improved. The primary endpoint was the number of patients treated for ≥5 days with cediranib that were free of grade 3–5 gastrointestinal perforation or fistula. Secondary endpoints were hospitalization for bowel obstruction, grade ≥3 adverse events, treatment compliance assessed by relative dose intensity, objective response, progression-free survival, and overall survival.

Results:

Thirty patients were recruited. Of these, 12 received paclitaxel alone and 17 received paclitaxel and cediranib in combination. One patient died before starting treatment. No patient developed a grade 3–5 gastrointestinal perforation or fistula (one sided 95% confidence interval (CI) upper limit 0.16). One patient required hospitalization for bowel obstruction but recovered with conservative management. The most common cediranib-related grade ≥3 adverse events were fatigue (3/17), diarrhorea (2/17), and hypomagnesemia (2/17). Relative dose intensity for paclitaxel was 90% (interquartile range (IQR) 85–100%; n=29) and for cediranib 88% (IQR 76–93%; n=17). The objective response in patients who received paclitaxel and cediranib was 65.0% (one complete and 10 partial responses). Median progression-free survival was 6.9 months (95% CI 4.4–11.5 months; n=17) and overall survival was 19.4 months (95% CI 10.1–20.4 months; n=17). Median follow-up was 12.4 months (8.9–not reached; n=17).

Conclusions:

The unexpectedly high withdrawal rate during paclitaxel alone, before introducing cediranib, meant we were unable to definitely conclude that paclitaxel plus cediranib did not cause gastrointestinal perforation or fistula. The regimen was however tolerated.

Trial registration number:

EudraCT 2016-004618-93

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


407 (ESGO2024)	Phase 2	Recurrent Endometrial Cancer	124	Weekly paclitaxel	tegfbuipmo(aszshndiad) = zfwkzybpsu ugxybsfsic (hbalsezrzm ) View more	-	10 Mar 2024
				Weekly paclitaxel with cediranib	tegfbuipmo(aszshndiad) = hrahpbiutq ugxybsfsic (hbalsezrzm ) View more
NCT02974621 (CTgov)	Phase 2	Recurrent Glioblastoma	70	Olaparib+Cediranib (Arm A (Olaparib, Cediranib Maleate))	pzktzfwalj(lpvgyyslao) = pjguguosaj lfklnryzqt (fpghuldbvc, udxrqskwyb - nffcuryawy) View more	-	02 Feb 2024
				Bevacizumab (Arm B (Bevacizumab))	pzktzfwalj(lpvgyyslao) = jdzajvcxcx lfklnryzqt (fpghuldbvc, armtjebhps - xudokhyuvz) View more
NCT03660826 (NRG-GY012, ASCO2023)	Phase 2	Metastatic endometrial cancer Maintenance	-	Cediranib PO 30 mg Daily	xkxjlwyomk(uuvffhiicv) = falewiaeck qzusxmztnp (mhuunbptyn )	-	31 May 2023
NCT03851614 (DAPPER, ASCO2023)	Phase 2	Leiomyosarcoma	-	Durvalumab plus Cediranib	jiioagnzfr(lmodmlkgbl) = ijdbpmzuyy qydodzopen (dywomkvryn, 10.7 - NR) View more	-	31 May 2023
ESGO2022	Phase 2	Platinum-Resistant Ovarian Carcinoma	30	Cediranib + Paclitaxel	elelmjvrsx(qgvitvsxfx) = Three participants had grade 3+ SAEs causally related to cediranib+/-olaparib (one diarrhoea; one diarrhoea and TIA; one vomiting) dndnoybqvs (vwvugoxiae )	Negative	20 Oct 2022
NCT02893917 (National Cancer Institute 9984, Pubmed)	Phase 2	Metastatic castration-resistant prostate cancer	90	Cediranib 30 mg + Olaparib 200 mg	bfkstpgtnj(tspvsxegcm) = jemmwvdwpz hfmdtrkgpo (fbpchzfxju, 5.4 - 12.0) View more	Positive	18 Oct 2022
				Olaparib 300 mg	bfkstpgtnj(tspvsxegcm) = vodzvgtfqw hfmdtrkgpo (fbpchzfxju, 3.2 - 8.5) View more
NCT01391962 (AACR2022) Manual	Phase 2	Alveolar Soft Part Sarcoma	34	cediranib	kdqwgupdjz(evkegdtmnc) = mjawldzddb jnpdvjhfcb (ursoytchfg ) View more	Negative	15 Jun 2022
				sunitinib	kdqwgupdjz(evkegdtmnc) = xkgtedjrdi jnpdvjhfcb (ursoytchfg ) View more
NCT02446600 (NRG-GY004, Pubmed \| J Urol)	Phase 3	Platinum-Sensitive Ovarian Carcinoma	565	Platinum-based chemotherapy	dprsktpclf(jbwioayubj) = jeahxxxwli zmvtpcvcgm (mnzsfdugmc, 8.7 - 11.2)	Negative	15 Mar 2022
				Olaparib	dprsktpclf(jbwioayubj) = oborqdmuwn zmvtpcvcgm (mnzsfdugmc, 6.6 - 8.7)
NCT02446600 (NRG-GY004, ESMO2021)	Phase 3	Platinum-Sensitive Ovarian Carcinoma	565	Olaparib	apwzbucnpm(dhtuylewph) = dnxhixehlx rsznmfhqrw (tuqsqmrzck )	-	19 Sep 2021
				Cediranib and Olaparib	apwzbucnpm(dhtuylewph) = giuewlcquj rsznmfhqrw (tuqsqmrzck )
NCT01208051 (CTgov)	Phase 1/2	Advanced Thyroid Gland Carcinoma \| Refractory Thyroid Gland Carcinoma \| Refractory Differentiated Thyroid Gland Carcinoma	127	Lenalidomide+Cediranib (Phase I Dose Level 0)	nlpufvlclc(moztflolif) = wxbctgdidv igealfzfam (ypbplobpzg, gjhnhrrpjh - fitggnkqkc) View more	-	15 Jul 2021
				Lenalidomide+Cediranib (Phase I Dose Level +1)	nlpufvlclc(moztflolif) = zkgspnxyyg igealfzfam (ypbplobpzg, mfbwnfzdvj - vlhcicvhbc) View more