A Multinational Double-Blind, Randomized Phase IIb Cooperative Group Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo when Administered in Combination with Chemotherapy and/or Endocrine Therapy in Patients with Locally Recurrent or Metastatic Breast Cancer

Conditions: ocally recurrent of metastatic breast cancer
MedDRA version: 14.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2007-001416-23-DE

Lead Sponsor: FONDAZIONE MICHELANGELO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 220

Inclusion Criteria

1.Femal patients with 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 =18 years. Women who are ER+ or PgR+ and candidates for endocrine therapy, must be post-menopausal as defined below:
•Bilateral oophorectomy; or
•No menses for at least 12 months in patients with an intact uterus, not on gonadatropin suppressing agents; or
•Follicle-stimulating hormone (FSH) in postmenopausal range in patients <60 years without prior hysterectomy; or
•Pre-menopausal women undergoing pharmacological ovarian ablation.
4.Any adjuvant or neoadjuvant taxane therapy must have been completed at least 12 months prior to randomization should the patient be candidate to start present study treatment with chemotherapy.
5.Patients must have discontinued other adjuvant chemotherapy at least 3 weeks prior to randomization.
6.Adjuvant aromatase inhibitors must have been completed at least 3 months prior to randomization.
7.Adjuvant tamoxifen must have been completed at least 4 weeks prior to randomization
8.Prior radiation therapy is allowed but must be completed at least 3 weeks prior to randomization, with all acute toxicities recovered to baseline status. Previously radiated area(s) must not be the only site of disease and must not correspond to more than 25% of the bone marrow producing areas for patients who are candidate for chemotherapy.
9.ECOG Performance Status of 0 or 1 (see Appendix A).
10.Adequate bone marrow, liver, and renal function as assessed by the following:
•Hemoglobin >=9.0 g/dl
•Absolute neutrophil count (ANC) >= 1,500/mm3
•Platelet count >= 100,000/mm3
•Total bilirubin <= 1.5 times the upper limit of normal (ULN)
•Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 x ULN (<= 5 x ULN for patients with liver involvement)
•International Normalized Ratio for Prothrombin Time (PT-INR) <=1.5 and activated prothrombin time (aPTT) within normal limits.
•Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib/placebo and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
•Creatinine <= 1.5 times the upper limit of normal.
11.Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization, and patients must agree to use adequate contraception (barrier method of birth control) prior to randomization, for the duration of study participation, and for 28 days after the last dose of study treatment.
12.Patients must be willing and able to sign a written informed consent. A signed informed consent must be appropriately obtained prior to any study specific procedures.
13.Patients must be able to swallow, retain, and absorb whole oral tablets

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

1.Patients with breast cancer over-expressing human epidermal growth factor receptor 2 (HER2) [gene amplification by fluorescence in situ hybridization (FISH) or 3+ over-expression by immunohistochemistry (IHC)]. Patients with unknown HER-2 status are not eligible.
2.Patients with active brain metastases. Patients with neurological symptoms must undergo a contrast CT scan or MRI of the brain to exclude active brain metastasis. Patients with treated brain metastases are eligible provided they have no evidence of disease and are off definitive therapy (including steroids) at least 3 months prior to randomization.
3.Prior chemotherapy or endocrine therapy for locally recurrent or metastatic breast cancer.
4.Patients with unknown hormone receptor status.
5.Patients who are ER+ or PgR+ and are pre-menopausal and unwilling to undergo pharmacological ovarian ablation
6.Women who are pregnant or breast-feeding.
7.Major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization.
8.Evidence or history of bleeding diathesis or coagulopathy.
9.Serious, non-healing wound, ulcer, or bone fracture.
10.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.
11.Pre-existing peripheral neuropathy =Grade 2.
12.Use of cytochrome P450 enzyme-inducing anti-epileptic drugs (such as phenytoin, carbamazepine, or phenobarbital) is not allowed.
13.Cardiac disease:
•Congestive heart failure >class II New York Heart Association (NYHA) (See Appendix B), or
•Unstable angina (anginal symptoms at rest), or new-onset angina (begun within the last 3 months), or myocardial infarction within the 6 months prior to randomization, or
•Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
14.Uncontrolled hypertension (systolic blood pressure >150 mm Hg or diastolic pressure >90 mm Hg) despite optimal medical management.
15.Thrombolic, embolic, venous, or arterial events, such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
16.Pulmonary hemorrhage/bleeding event >National Cancer Institute (NCI-CTCAE) Grade 2 within 4 weeks of first dose of study drug.
17.Any other hemorrhage/bleeding event =NCI-CTCAE Grade 3 within 4 weeks of randomization.
18.Active clinically serious infection >NCI-CTCAE Grade 2.
19.Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
20.Previous or concurrent cancer that is distinct in primary site or histology from breast cancer EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis], or any cancer curatively treated >5 years prior to randomization.
21.Known or suspected allergy to sorafenib, letrozole or hypersensitivity to docetaxel or drugs using the vehicles polysorbate 80 or ethanol.
22.Prior or concurrent use of St. John’s Wort or rifampin (rifampicin) within 1 week of randomization.
23.Prior or concurrent treatment with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors (VEGFR) (licensed or investigational).
24.Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding randomization.