A Randomized, Partially Blinded, Phase II Study to Assess the Safety, Tolerability, and Efficacy of ZD6474 Alone or in Combination with Paclitaxel and Carboplatin in Subjects with Previously Untreated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) - 6474IL0007

• Conditions: on Small Cell Lung Cancer

• Registration Number: EUCTR2004-000379-32-FI
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-07-08
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

For inclusion in the study, patients must fulfill all of the following criteria:

1.Provision of written informed consent;

2.Age 18 years or older;

3.Histologically or cytologically confirmed locally advanced (Stage IIIb with pleural effusion) or metastatic (Stage IV) NSCLC with no evidence of mixed small cell and non-small cell histology. (Patients with previously resected early stage non-small cell lung cancer (Stages I-III) who have relapsed and have not been treated with chemotherapy or radiotherapy are also eligible);

4.Considered suitable for first line treatment of NSCLC with paclitaxel/carboplatin and ZD6474 with no prior chemotherapy, biological therapy, or radiation therapy, not including adjuvant or neoadjuvant therapy, radiation to the brain, or radiation to a bone metastasis for palliation;

5.One or more measurable lesions at least 10 mm in the longest diameter by spiral CT scan or 20 mm with conventional techniques (according to RECIST);

6.WHO performance status 0 or 1;

7.Life expectancy of more than 12 weeks.

PET inclusion (for selected centers)

1.One or more measurable lesions greater than 20mm diameter (by spiral CT or conventional CT) in all dimensions to be followed as target lesions on RECIST;

2.The whole lesion and the left ventricle or aorta must be in the same field of view for the PET;

3.Fasting blood glucose < 150 mg/dL at baseline;

4.In the clinical judgment of the investigator, the patient will be able to comply with the requirements of PET imaging (i.e., lie on the couch with arms up for the duration of the study).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Any of the following is regarded as a criterion for exclusion from the study:

1.Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 1 week;

2.Currently active skin disease, i.e., acne, psoriasis, eczema;

3.Currently active gastrointestinal disease that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea;

4.History of clinically significant hemoptysis in the past 3 months;

5.Neutrophils less than 1.5 x 109/L (1,500/mm3) or platelets less than 100, 000/mm3;

6.Serum bilirubin >1.5 x the upper limit of reference range (ULRR);

7.Creatinine clearance < 30 ml/min, calculated from serum creatinine;
8.ALT or AST greater than 2.5 x ULRR if no demonstrable liver metastases; ALT or AST greater than 5.0 x ULRR if judged by the investigator to be related to liver metastases;

9.Alkaline phosphatase greater than 2.5 x ULRR;

10.Potassium concentration less then 3.5mEq/L, calcium (ionized calcium or adjusted for albumin) or magnesium concentrations outside normal limits. Supplementation of electrolytes is permitted;

11.History of chronic atrial fibrillation or clinically significant arrhythmia (multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE grade 3) or a symptomatic sustained ventricular tachycardia;

12.Significant cardiac event (including symptomatic heart failure or symptomatic angina) within 3 months of entry; or any cardiac disease that in the opinion of the investigator increases risk of ventricular arrhythmia;

13.Previous history of QT prolongation while taking other medication unless agreed between the investigator and AstraZeneca;

14.Congenital long QT syndrome;

15.QT with Bazett’s correction unmeasurable or 460 msec or greater on screening ECG (Note for the randomized phase only: If a patient has QTc of 460 msec or greater on screening ECG, the screening ECG may be repeated, at least 24 hours after the first ECG. The average QTc from the two screening ECGs must be less than 460 msec in order for the patient to be eligible for the study. If the patient meets eligibility requirements, the baseline” QTc for this patient will be the average of the three ECGs (screen 1, screen 2, and pre-1st dose));

16.Superior Vena Cava (SVC) syndrome;

17.Left ventricular ejection fraction (LVEF) less than 45% measured by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) for patients with previous anthracycline therapy (total dose > 450 mg/m2) or significant cardiovascular disease or chest irradiation;

18.Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mg Hg);

19.Any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol;

20.Any pre-study or concomitant therapy as outlined in Section 3.5.4 of the protocol unless agreed between the investigator and AstraZeneca;

21.Participation in an investigational trial within the past 30 days;

22.Women of childbearing potential with a positive pregnancy test prior to receiving trial medication or breast-feeding women;

23.Men or women unwilling to use an acceptable method of contraception while on study;

24.Patients with co-existing malignancies diagnosed within the last 5 years

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified