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

Phase 1

Conditions: non small cell lung cancer
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2004-000379-32-ES

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

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
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

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. Previous or current malignancies at other sites within last 5 years, with the exception of in situ carcinoma of the cervix and adequately treated basal cell or squamous cell carcinoma of

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: time to progression (TTP). a comparasion will be made of ZD6474 alone (300 mg PO daily), ZD6474 in combination with paclitaxel/carboplatino, and paclitaxel/ carboplatino alone;Secondary Objective: The secondary objectives of the randomized phase are the following: Tumor response rates, safety and tolerability, Quality of Life, survival, pharmacokinetics Comparisions will be made of ZD6474 alone (300 mg PO daily), ZD6474 in combination with paclitaxel/carboplatin, and paclitaxel/carboplatin alone;Primary end point(s): The primary endpoint is efficacy (for all treatment arms), defined as time to tumour progression, which will be assessed regularly, using RECIST criteria;Timepoint(s) of evaluation of this end point: NA

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: The secondary objective of the safety run-in phase is to explore the pharmacokinetics of ZD6474, paclitaxel, and carboplatin administered alone and in combination in patients with previously untreated locally advanced or metastatic NSCLC, and to compare these parameters with the existing AstraZeneca database. Additionally, the survival of patients will be assessed.;Secondary end point(s): NA

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