Non Small Cell Lung Cancer
Conditions
Interventions
Product Name: ZD6474 Tablets
Product Code: ZD6474
Pharmaceutical Form: Tablet
CAS Number: 338992-00-0
Current Sponsor code: ZD6474
Concentration unit: mg milligram(s)
Concentration type: equal
Concent
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Time to progression (TTP). A comparision will be made of ZD6474 alone (300 mg PO daily), ZD6474 in combination with paclitaxel/carboplatin, and paclitaxel/carboplatin 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 study will be conducted in two parts. The run-in phase (which is being conducted in the USA) will determine the dose of ZD6474 to be used in combination with paclitaxel + carboplatin chemotherapy. The randomised phase (to be conducted in the EU and elsewhere) will then use a 3 arm design with a 2:1:1 randomisation scheme to the following study arms Arm 1; ZD6474 300mg alone Arm 2; ZD6474 (dose to be determined from run-in phase) plus chemotherapy Arm 3; Matched placebo to ZD6474 plus chemotherapy For arms 2 and 3, chemotherapy is defined as Paclitaxel (200 mg/m2) administered IV over 3 hours in Cycle 1 and over 60-90 minutes in all subsequent cycles, once every 3 weeks plus carboplatin (AUCSS 6) administered IV over 30-60 minutes in all cycles, once every 3 weeks. A maximum of 6 cycles of chemotherapy will be administered, after which time (if subjects have not progressed), subjects will continue on either ZD6474 or matched placebo alone. The study is partially blinded - investigators and subjects in arm 1 will be aware that this arm is ZD6474 monotherapy, but arms 2 and 3 will be double blind The primary endpoint is efficacy (for all treatment arms), defined as time to tumour progression, which will be assessed regularly, using RECIST criteria | — |
Countries
Finland, Italy, Spain
Outcome results
None listed