A study to determine the safety and activity of Sorafenib in patients with locally recurrent or metastatic breast cancer
- Conditions
- Health Condition 1: null- Patients with locally recurrent or metastatic breast cancer
- Registration Number
- CTRI/2008/091/000017
- Lead Sponsor
- William J Gradishar Feinberg School of MedicineChicago Illinois USA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 220
Note: No upper age limit for this clinical trial, (indicated as 18 years and above)
1.Histologically or cytologically confirmed adenocarcinoma of the breast.
2.Measurable or evaluable locally recurrent or metastatic disease. (Locally recurrent disease must not be amenable to resection with curative intent.) All scans used to document measurable or evaluable disease must be done within 4 weeks prior to randomization.
3.Age greater than or equal to 18 years
4.Patients must not have had adjuvant or neoadjuvant taxane therapy within 12 months of randomization.
5.Patients must have discontinued other adjuvant chemotherapy at least 3 weeks prior to randomization.
6.Prior hormonal therapy for locally recurrent or metastatic disease is allowed.
7.Prior radiation therapy is allowed but must be completed at least 3 weeks prior to randomization. Previously radiated area(s) must not be the only site of disease.
8.ECOG Performance Status of 0 or 1
9.Adequate bone marrow, liver, and renal function as assessed by the following:
- Hemoglobin greater than or equal to 9.0 g/dl
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3
- Platelet count greater than or equal to100,000/mm3
- Total bilirubin less than or equal to 2.0 times the upper limit of normal
- ALT and AST less than or equal to 2.5 x upper limit of normal (less than or equal to 5 x upper limit of normal for patients with liver involvement)
- International Normalized Ratio for Prothrombin Time (PT-INR) and activated partial prothrombin time (aPTT) less than or equal to 1.5 times the upper limit of normal for patients NOT on blood thinners. NOTE: Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin will have a higher value but may be allowed to participate as long as the INR is measured prior to initiation of sorafenib/placebo and is monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Creatinine less than or equal to 2.0 times the upper limit of normal
10.Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization and must agree to use adequate contraception prior to randomization and for the duration of study participation.
11.Patients must be able and willing to sign a written informed consent. A signed informed consent must be appropriately obtained prior to any study specific procedures.
12.Patients must be able to swallow and retain oral medication.
1.Patients with breast cancer over-expressing HER-2 (gene amplification by FISH or 3+ over-expression by immunohistochemistry). Patients with unknown HER-2 status are not eligible.
2.Patients with active brain metastases. Patients with neurological symptoms must undergo a contrast computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain to exclude active brain metastasis. Patients with treated brain metastases are eligible provided they have no evidence of brain disease and are off definitive therapy (including steroids) within 3 months prior to randomization.
3.Prior chemotherapy for locally recurrent or metastatic breast cancer
4.Major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization
5.Evidence or history of bleeding diathesis or coagulopathy
6.Serious, non-healing wound, ulcer, or bone fracture
7.Substance abuse, or medical, psychological, or social condition that may interfere with the patient?s participation in the study or evaluation of the study results
8.Pre-existing peripheral neuropathy ≥Grade 2
9.Use of cytochrome P450 enzyme-inducing anti-epileptic drugs (such as phenytoin, carbamazepine, or phenobarbital)
10.Clinically significant cardiac disease including congestive heart failure > class II NYHA (see Appendix IV), unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months), myocardial infarction within the past 6 months prior to randomization
11.Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy and or uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg) despite optimal medical management
12.Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. No pulmonary hemorrhage/bleeding event > NCI-CTCAE Grade 2 within 4 weeks of randomization. No other hemorrhage/bleeding event greater than or equal to CTCAE Grade 3 within 4 weeks of randomization
13.Active clinically serious infection > NCI-CTCAE Grade 2
14.Known human immunodeficiency virus infection or chronic hepatitis B or C
15.Previous or concurrent cancer that is distinct in primary site or histology from breast cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis].
16.Known or suspected allergy to sorafenib or hypersensitivity to paclitaxel or drugs using the vehicle Cremophor
17.Use of St. John?s Wort or rifampin (rifampicin) within 1 week of randomization
18.Prior treatment with bevacizumab or any other drugs (licensed or investigational) that target VEGF or VEGF-R
19.Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy or tumor embolization) other than paclitaxel and sorafenib/placebo
20.Women that are pregnant or breast feeding
21.Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding randomization
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare progression free survival (PFS) in patients with sorafenib and paclitaxel versus patients treated with placebo and paclitaxel as a first-line therapy for locally recurrent or metastatic breast cancerTimepoint: Events projected to occur November 2008
- Secondary Outcome Measures
Name Time Method 1.To compare the objective response rate, duration of response, time to progression, and survival of patients treated with sorafenib and paclitaxel versus placebo and paclitaxel.<br>2.To compare the safety of patients treated with sorafenib and paclitaxel versus placebo and paclitaxel<br>Timepoint: Overall survival events projected to occur August 2010