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Efficacy Study Comparing ZD6474 in Combination With Pemetrexed and Pemetrexed Alone in 2nd Line NSCLC Patients

Information source: AstraZeneca
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non Small Cell Lung Cancer; Lung Cancer

Intervention: Vandetanib (Drug); Pemetrexed (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Peter Langmuir, MD, Study Director, Affiliation: AstraZeneca
Richard de Boer, MD, Principal Investigator, Affiliation: Western Hospital Footscray


Non-small cell lung cancer (NSCLC) can be treated with drugs that kill tumour cells, stop them from dividing, or stop the growth of the blood supply that cancers need to grow and spread. Clinical research has shown that drugs that inhibit vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor (EGFR) signalling can increase overall survival in patients with advanced non-small cell lung cancer (NSCLC). Preclinical studies have shown that vandetanib (ZD6474) is an inhibitor of both VEGFR and EGFR signalling. Giving vandetanib may therefore inhibit the growth of cancer cells by blocking their blood supply and by stopping them from dividing. This lung cancer study is to investigate if adding vandetanib to Alimta (pemetrexed) is more effective than Alimta (pemetrexed) alone.

Clinical Details

Official title: A Phase III, Randomized, Double-Blinded, Parallel Group, Multi-Centre Study to Assess the Efficacy and Safety of ZD6474 (ZACTIMA™) in Combination With Pemetrexed (Alimta®) Versus Pemetrexed Alone in Patients With Locally-Advanced or Metastatic NSCLC

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Demonstrate an improvement in progression-free survival for the combination of ZD6474 (vandetanib) plus pemetrexed compared with pemetrexed plus placebo in patients with locally advanced or metastatic NSCLC after failure of 1st line anti-cancer therapy

Secondary outcome: Demonstrate an improvement in overall survival for ZD6474 (vandetanib) in combination with pemetrexed compared with pemetrexed plus placebo

Detailed description: This randomized phase III non-small cell lung cancer clinical trial is studying the effect of Alimta (pemetrexed) plus vandetanib to see how well the combination works compared to Alimta (pemetrexed) alone in patients who have previously been treated for non-small cell lung cancer (NSCLC).


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Provision of informed consent

- Female or male aged 18 years or above

- Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (stage

IIIB or IV) on entry into study

- Failure of 1st line anti-cancer therapy (either radiological documentation of disease

progression or due to toxicity) or subsequent relapse of disease following 1st line therapy

- WHO Performance status 0 - 2

- One or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral

CT scan or 20 mm with conventional techniques according to RECIST criteria. Previously irradiated lesions will not be considered measurable.

- Life expectancy of 12 weeks or longer

- Negative pregnancy test for women of childbearing potential only

Exclusion Criteria:

- Mixed small cell and non-small cell lung cancer histology

- Patients have received 2nd-line or subsequent anti-cancer therapy

- Prior treatment with pemetrexed

- Prior treatment with VEGFR TKIs (previous treatment with bevacizumab [Avastin] is


- Known or suspected brain metastases or spinal cord compression, unless treated at

least 4 weeks before entry, and stable without steroid treatment for 10 days

- The last radiation therapy within 4 weeks before the start of study therapy, not

including local palliative radiation

- The last dose of prior chemotherapy or other anti-cancer therapy is discontinued less

than 3 weeks before the start of study therapy (6 weeks for nitrosoureas, mitomycin, and suramin)

- Major surgery within 4 weeks before entry, or incompletely healed surgical incision

- Neutrophils <1. 5 x 109/L or platelets <100 x 109/L

- Serum bilirubin >1. 5 x the upper limit of reference range (ULRR)

- Creatinine clearance <50 ml/min calculated by either Cockcroft -Gault, 24 hours urine

collection, EDTA scan or other validated methods

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2. 5 x ULRR in the

absence of liver metastases, or > 5 x ULRR in the presence of liver metastases

- Alkaline phosphatase (ALP) >2. 5 x ULRR in the absence of liver metastases, or >5 x

ULRR in the presence of liver metastases

- Current active gastrointestinal disease that may affect the ability of the patient to

absorb ZD6474 or tolerate diarrhoea

- Evidence of severe or uncontrolled systemic disease or any concurrent condition which

in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol

- Any unresolved toxicity greater than CTCAE Grade 2 from previous anti-cancer therapy

- Significant cardiovascular event (e. g., myocardial infarction, superior vena cava

[SVC] syndrome), New York Heart Association [NYHA] classification of heart disease ≥2 within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia

- History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy,

trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded

- Congenital long QT syndrome or 1st degree relative with unexplained sudden death under

40 years of age

- QT prolongation with other medications that required discontinuation of that


- Presence of left bundle branch block (LBBB)

- QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG (Note: If a

patient has QTc interval ≥480 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]. The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study) Patients who are receiving a drug that has a risk of QTc prolongation are eligible if QTc is <460 msec.

- Potassium <4. 0 mmol/L despite supplementation; serum calcium (or ionized or adjusted

for albumin), or magnesium out of normal range despite supplementation

- Women who are pregnant or breast-feeding

- Any concomitant medications that may cause QTc prolongation or induce Torsades de

Pointes or induce CYP3A4 function. Drugs that have a risk of QTc prolongation, that in the investigator's opinion cannot be discontinued, are allowed, but only of the QTc is <460 msec

- Hypertension not controlled by medical therapy (systolic blood pressure greater than

160 millimetre of mercury [mmHg] or diastolic blood pressure greater than 100 mmHg)

- Previous or current malignancies of other histologies within the last 5 years, with

the exception of in situ carcinoma of the cervix and adequately treated basal cell or squamous cell carcinoma of the skin

- Treatment with a non-approved or investigational drug within 30 days before Day 1 of

study treatment

- Concomitant use of yellow fever vaccine or any live attenuated vaccines

Locations and Contacts

Research Site, CIUDAD DE BUENOS AIRES, Argentina

Research Site, BUENOS AIRES, Argentina

Research Site, C�RDOBA, Argentina

Research Site, SALTA, Argentina

Research Site, SANTA FE, Argentina

Research Site, BRUSSELS (WOLUW�-ST-LAMBERT), Belgium

Research Site, LEUVEN, Belgium

Research Site, LI�GE, Belgium

Research Site, BOGOTA, Colombia

Research Site, MEDELL�N, Colombia

Research Site, AVIGNON, France

Research Site, LYON CEDEX 04, France

Research Site, PARIS, France

Research Site, PONTOISE CEDEX, France

Research Site, STRASBOURG CEDEX, France

Research Site, HANNOVER, Germany

Research Site, KARLSRUHE, Germany

Research Site, KASSEL, Germany

Research Site, K�LN, Germany

Research Site, LEIPZIG, Germany

Research Site, N. FALIRO, Greece

Research Site, PATRAS, Greece

Research Site, THESSALONIKI, Greece

Research Site, HONG KONG, Hong Kong

Research Site, BEER-SHEEVA, Israel

Research Site, HAIFA, Israel

Research Site, JERUSALEM, Israel

Research Site, PETACH-TIKVA, Israel

Research Site, SAFED, Israel

Research Site, TEL-AVIV, Israel

Research Site, TEL-HASHOMER, Israel

Research Site, ROMA, Italy

Research Site, AGUASCALIENTES, Mexico

Research Site, PASAY CITY, Philippines

Research Site, QUEZON CITY, Philippines

Research Site, CEBU CITY, Philippines

Research Site, Manilla, Philippines

Research Site, LISBOA, Portugal

Research Site, SANTA MARIA DA FEIRA, Portugal

Research Site, SET�BAL, Portugal

Research Site, CAPE TOWN, South Africa

Research Site, DURBAN, South Africa

Research Site, PORT ELIZABETH, South Africa

Research Site, PRETORIA, South Africa

Research Site, LUND, Sweden

Research Site, SUNDSVALL, Sweden

Research Site, UME�, Sweden

Research Site, UPPSALA, Sweden

Research Site, TAIPEI, Taiwan

Research Site, BIRMINGHAM, United Kingdom

Research Site, EDINBURGH, United Kingdom

Research Site, LEEDS, United Kingdom

Research Site, MANCHESTER, United Kingdom

Research Site, WOLVERHAMPTON, United Kingdom

Research Site, ZERIFIN, 1516339, Israel

Research Site, KFAR SABA, 44281, Israel

Research Site, M�LAGA, ANDALUC�a, Spain

Research Site, Gujarat, Ahmedabad, India

Research Site, CASA GRANDE, Arizona, United States

Research Site, CHANDLER, Arizona, United States

Research Site, AVELLANEDA, Buenos Aires, Argentina

Research Site, LA PLATA, Buenos Aires, Argentina

Research Site, RAMOS MEJ�A, Buenos Aires, Argentina

Research Site, MATAR�(BARCELONA), CATALU�a, Spain

Research Site, MADRID, Comunidad De Madrid, Spain

Research Site, FARMINGTON, Connecticut, United States

Research Site, STAMFORD, Connecticut, United States

Research Site, MEXICO, D.F., Mexico

Research Site, WASHINGTON, District of Columbia, United States

Research Site, VALENCIA, Estado Carabobo, Venezuela, Venezuela

Research Site, ORLANDO, Florida, United States

Research Site, A CORU�A, GALICIA, Spain

Research Site, LUGO, GALICIA, Spain

Research Site, ORENSE, GALICIA, Spain



Research Site, GENOVA, GE, Italy

Research Site, GAINESVILLE, Georgia, United States

Research Site, SKOKIE, Illinois, United States

Research Site, SIOUX CITY, Iowa, United States

Research Site, MT. STERLING, Kentucky, United States

Research Site, MILANO, MI, Italy

Research Site, PORTLAND, Maine, United States

Research Site, BALTIMORE, Maryland, United States

Research Site, BOSTON, Massachusetts, United States

Research Site, CARACAS, Municipio Libertador, Venezuela

Research Site, RANDWICK, New South Wales, Australia

Research Site, ST. LEONARDS, New South Wales, Australia

Research Site, MINEOLA, New York, United States

Research Site, ROCHESTER, New York, United States

Research Site, WINSTON-SALEM, North Carolina, United States

Research Site, MIDDLETOWN, Ohio, United States

Research Site, CHERMSIDE, Queensland, Australia

Research Site, HILTON HEAD ISLAND, South Carolina, United States

Research Site, AUSTIN, Texas, United States

Research Site, SALT LAKE CITY, Utah, United States

Research Site, CALI, VALLE, Colombia

Research Site, Tamil Nadu, Vellore, India

Research Site, FITZROY, Victoria, Australia

Research Site, FOOTSCRAY, Victoria, Australia

Research Site, HEIDELBERG, Victoria, Australia

Research Site, WODONGA, Victoria, Australia

Research Site, V�STER�S, V�Stmanlands L�N, Sweden

Research Site, ORBASSANO, to, Italy

Additional Information

AstraZeneca Clinical Trial Information - Outside US

Starting date: January 2007
Ending date: July 2008
Last updated: June 12, 2008

Page last updated: June 20, 2008

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