Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study of AG-013736 in Combination With Docetaxel Versus Docetaxel Alone in Patients With Metastatic Breast Cancer Preceded by a Phase 1 Evaluation of the Combinatio
- Conditions
- Metastatic breast cancer not previously treated with chemotherapy.MedDRA version: 5.1Level: PTClassification code 10055113
- Registration Number
- EUCTR2004-000971-33-CZ
- Lead Sponsor
- Pifzer Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 168
1. female patients with histologically/cytologically proven metastatic breast carcinoma (Stage IV, or recurrent with local or regional spread or distant metastatic disease)
2. no prior chemotherapy for metastatic disease. (If chemotherapy given in the adjuvant setting, then the patient must have completed chemotherapy at least 12 months before the first documentation of metastatic disease. Patients who received adjuvant therapy with a taxane [paclitaxel or docetaxel] are eligible.)
3. at least 1 target lesion, as defined by RECIST (see Protocol Appendix C)
4. adequate bone marrow function as defined by:
- ANC =1500 cells/mm3
- platelets =100, 000 cells/mm3
- Hgb =10 g/dL
5. adequate liver function as defined by:
- bilirubin =upper limit of normal (ULN)
- AST and ALT =2.5 x ULN if alkaline phosphatase is =ULN, or alkaline phosphatase may be up to 4 x ULN if aminotransferases are =ULN. (Patients with aminotransferase elevation >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN should not be entered due to the decreased clearance of docetaxel and increased risk of toxicity.)
6. adequate renal function as defined by both:
- serum creatinine =1.5 mg/dL
- =500 mg urinary protein/24 hours or dipstick <1+
7. no evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart (The baseline systolic blood pressure readings must be less than or equal to 140 mm Hg, and the baseline diastolic blood pressure readings must be less than or equal to 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible)
8. ECOG performance status of 0, 1, or 2 (See Protocol Appendix D)
9. life expectancy =12 weeks
10. adults =18 years of age
11. negative serum or urine pregnancy test for patients of child-bearing potential
12. written informed consent
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
1. adjuvant chemotherapy given within the past 12 months or prior chemotherapy for metastatic disease
2. current use or anticipated need for drugs that are known CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine) during the course of study
3. current use or anticipated need for drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St John’s wort) during the course of study. (Note: the use of dexamethasone as part of the docetaxel dosing regimen is not an exclusion criterion)
4. requirement of anticoagulant therapy except for low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis (DVT)
5. uncontrolled brain metastases (a controlled brain metastasis must be previously treated, asymptomatic, and without growth for 4 months)
6. clinically significant gastrointestinal abnormalities including the following:
- inability to take oral medication
- requiring intravenous alimentation
- malabsorption syndrome
- requiring treatment of active ulcer disease in the past 6 months
- prior gastric resection
- active gastrointestinal bleeding, unrelated to cancer, as evidenced by either hematemesis, hematochezia, or melena in the past 3 months
7. history of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
8. major surgical procedure within 4 weeks of treatment for Phase 1 or randomization for Phase 2
9. unstable or severe intercurrent medical condition that, in the opinion of the investigator, might interfere with achievement of study objectives
10. psychological or sociological conditions, addictive disorders, or family problems, which would preclude compliance with the protocol
11. history of a malignancy (other than breast cancer) except those patients treated with curative intent for skin cancer (other than melanoma) or in situ cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years
12. patients having procreative potential who are not using adequate contraception or practicing abstinence
13. women who are pregnant or breast-feeding
14. patients with proteinuria. (Patients with =1+ protein on urine dipstick at baseline should undergo a 24-hour urine collection. Results must demonstrate =500 mg of protein in 24 hours to allow participation in the study.)
15. known prior severe hypersensitivity reactions to agents containing polysorbate 80
16. patients with Her-2/Neu over-expression
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method