Fourth Phase III Study of Vandetanib (ZACTIMA(TM), ZD6474) in Patients With Advanced Lung Cancer

2007-02-26 21:35 1044

A Phase III international, parallel group, randomised, double-blind study of vandetanib in combination with pemetrexed for advanced non-small cell lung cancer (NSCLC) after failure of first line anti-cancer therapy

-- For Non-US Healthcare Professional Press Only --

ALDERLEY PARK, Cheshire, Feb. 26 /Xinhua-PRNewswire/ -- AstraZeneca today announced that a new Phase III study of novel once-daily oral anti-cancer drug, vandetanib (ZACTIMA(TM), ZD6474), is underway. The study - Study 36 - will investigate the addition of vandetanib to pemetrexed (Alimta(R)) as second line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of first line anti-cancer treatment. Study 36 will be conducted across 20 countries worldwide, and is expected to enrol at least 508 patients.

As its primary objective, Study 36 will evaluate progression-free survival with vandetanib 100mg plus pemetrexed 500mg/m2 compared with pemetrexed 500mg/m2 plus placebo in patients with advanced NSCLC, who have previously received anti-cancer treatment. The study will also assess overall survival, objective response rate, disease control rate, duration of response, effect on disease related symptoms, time to deterioration of disease-related symptoms, the safety and tolerability of vandetanib in combination with pemetrexed, and population pharmacokinetics of vandetanib

Study 36's Principal Investigator, Dr. Richard de Boer, Western Hospital, Victoria, Australia, commented "After treatment failure with initial therapy, response rates to further treatment is low in patients with advanced non-small cell lung cancer. The effect of combining novel targeted agents such as vandetanib with chemotherapy needs to be explored to progress treatment options for patient benefit."

Study 36 forms part of an extensive ongoing clinical development programme for vandetanib in NSCLC and is the fourth Phase III study in this tumour; the other three studies are:

-- Study 32 - a randomised, double-blind study, comparing

vandetanib 100mg in combination with docetaxel with docetaxel alone in

patients with locally advanced or metastatic NSCLC after failure of

first-line treatment.

-- Study 57 - a randomised, double-blind, study of vandetanib 300mg

monotherapy versus erlotinib 150mg in patients with advanced NSCLC

after failure of at least one, but no more that two, prior chemotherapy


-- Study 44 - a randomised, double-blind, placebo-controlled study

of vandetanib 300mg plus best supportive care (BSC) compared with

placebo plus BSC as third/fourth line treatment in patients with non-

small cell lung cancer (NSCLC) after treatment failure with

chemotherapy and an epidermal growth factor receptor tyrosine kinase

inhibitor (EGFR TKI).

Vandetanib (ZACTIMA(TM), ZD6474)

Vandetanib works by inhibiting both the development of the tumour's blood supply through inhibition of VEGFR (anti-angiogenesis) and the growth and survival of the tumour itself through inhibition of EGFR. It also inhibits RET kinase, an important growth factor in certain types of thyroid cancer. Vandetanib has shown promising anti-tumour activity in NSCLC when used alone and in combination with docetaxel in Phase II trials.(1,2) It has also shown encouraging early data in hereditary medullary thyroid cancer(3) and has been awarded FDA and EU orphan drug status, and FDA fast track designation for this indication. Vandetanib is currently in clinical development in a range of tumours.

ZACTIMA(TM) is a trademark of the AstraZeneca group of companies.

Notes to editors

-- Over 1.35 million new cases of lung cancer are diagnosed every year and nearly 1.2 million people die as a result of this devastating disease - more than breast, colon and prostate cancer combined.(4)

-- If lung cancer is detected at early stages, before it has spread to other organs or lymph nodes, around half of patients can survive for five years or more. However, few lung cancers are found at this early stage and it is normally diagnosed at the advanced stage, when five year survival falls to approximately 15%.(5)

-- AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of US$26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index.

-- For more information about AstraZeneca, please visit: .


(1) Natale RB et al. ZD6474 versus gefitinib in patients with advanced

NSCLC: Final results from a two-part, double-blind randomized phase II

trial. Proceedings of ASCO 2006; abstract no. 7000.

(2) Heymach JV et al. A phase II trial of ZD6474 plus docetaxel in

patients with previously treated NSCLC: Follow-up results. Proceedings

of ASCO 2006; abstract no. 7016.

(3) Wells S et al. A phase II trial of ZD6474 in patients with hereditary

metastatic medullary thyroid cancer. Proceedings of ASCO; abstract

no. 5533.

(4) Ferlay J et al. GLOBOCAN 2002: Cancer Incidence, Mortality and

Prevalence Worldwide IARC CancerBase No. 5. version 2.0, IARCPress,

Lyon, 2004.

(5) Bepler G. Lung cancer epidemiology and genetics. Journal of Thoracic

Imaging 1999;14(4):228-34.

Source: AstraZeneca