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Last Updated: 06/30/17

Information below provided by the Pharmaceutical Company.

Cediranib (AZD2171, RECENTIN)

Agent Description

Cediranib is a potent small molecule vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor of all three VEGF receptors (VEGFR-1, 2 and 3) at nanomolar concentrations. The Chemical name is 4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy] quinazoline maleate with a molecular mass of 566.59 as maleate salt (450.52 as free base). Cediranib tablets contain cediranib maleate, mannitol, dibasic calcium phosphate anhydrous, sodium starch glycolate, microcrystalline cellulose and magnesium stearate with a film coat containing hypromellose 2910, polyethylene glycol 400, red iron oxide, yellow iron oxide, black iron oxide and titanium dioxide.

Mechanism of Action

Cediranib is a potent VEGF receptor tyrosine kinase (RTK) inhibitor of all three VEGF Receptors (VEGFR-1, 2 and 3). Inhibition of VEGF signaling leads to the inhibition of angiogenesis, lymphangiogenesis, neo-vascular survival and vascular permeability. Cediranib also inhibits c-Kit tyrosine kinase based on steady-state free plasma concentrations achieved with 20 mg once daily in patients.

Classification

VEGF RTK inhibitor of VEGFR-1, 2, and 3

Molecular Targets

VEGFR-1, VEGFR-2, VEGFR-3, c-Kit

Monograph

On-going clinical trials for cediranib are listed on https://clinicaltrials.gov. Cediranib inhibited the growth of tumors in preclinical models in a dose-dependent manner. A reduction in micro-vessel density and metastasis was also observed in these preclinical models. Collectively, these changes indicate that cediranib limits tumor growth, metastases and microvascular permeability. Cediranib is not approved in any territory. Currently cediranib is being studied in phase III trials in combination with olaparib in patients with relapsed ovarian cancer. Phase II trials for the combination of cediranib and olaparib are also ongoing in other malignancies. Earlier phase I/II trials are ongoing for the combination of cediranib and durvalumab +/- olaparib.

Studies of Interest

Areas of interest:

Cediranib is being evaluated (planned/ongoing) across a broad array of malignancies. Focus of current development is combination regimens with other targeted therapies where it is demonstrated pre-clinically or based on translational science evidence of potential synergy of the combination. There is a preference of combining with existing AstraZeneca pipeline products.

Areas NOT of interest:

  • Combination of cediranib with chemotherapy is de-prioritized based on the results of already generated clinical trial data.
  • Cediranib as a monotherapy is developed in tumor types with strong signal of single agent activity, such as ASPS.

Information collaborator would like included in investigator proposals

Successful proposals will have:

  • strong scientific rationale and/or supporting pre-clinical data
  • study design containing clearly defined objectives and statistical validation to confirm they can be met
  • evidence of the Investigator's ability to deliver both the scientific and operational aspects of the proposal
  • consideration of safety, toxicity management and the overall risk-benefit in the proposed patient population.

Proposals will be evaluated on the overall safety and risk-benefit (evidence of consideration will be helpful), overlap with existing studies, and regulatory considerations.