BAY43-9006 - Phase II in Advanced Breast Cancer

Phase 2

Completed

Conditions: Breast Neoplasms
Breast Cancer

Interventions: Drug: Sorafenib (Nexavar, BAY43-9006)

Registration Number: NCT00101400

Lead Sponsor: Bayer

Brief Summary: The purpose of this study is to evaluate the anti-cancer activity and safety of BAY43-9006 (Sorafenib) in patients, who suffer from an advanced breast tumour, which has spread to other organs of body despite treatment that the patient has received so far.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 54

Inclusion Criteria

Age > 18 years
Women with prior histologically documented diagnosis of breast cancer
Subjects with metastatic disease who have already received and failed at least one chemotherapy regimen for metastatic disease and, if ER/PgR +ve, have failed on at least adjuvant hormonal therapy
Subjects for whom trastuzumab treatment is not indicated, no longer effective or refused by the subjects
Four weeks since the last cytotoxic chemotherapy or clear evidence of progression on hormonal therapy
Subjects who have at least one measurable lesion by CT (Computed Tomography) scan or MRI (Magnetic Resonance Imaging) according to modified WHO Tumour Response Criteria
Subjects who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0, 1 or 2
Adequate bone marrow, liver and renal function as assessed by the following laboratory evaluations:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) > 1,500/mm3
- Platelet count = 100,000/µl
- Total bilirubin =1.5 x the upper limit of normal.
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) = 2.5 x upper limit of normal (=5 x upper limit of normal for subjects with liver involvement of their cancer)
- Amylase and lipase = 1.5 x the upper limit of normal
- Serum creatinine = 3.0 x the upper limit of normal
- Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal (subjects who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate provided that no evidence of underlying abnormality in these parameters exists)
Subjects who give written informed consent prior to any study specific screening procedures with the understanding that the subject has the right to withdraw from the study at any time, without prejudice
Life expectancy of at least 12 weeks
Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria

Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma, or superficial bladder tumours [Ta, Tis and T1] or other malignancies curatively treated > 2 years prior to entry)
Congestive heart failure > New York Heart Association (NYHA) Class II
Cardiac arrhythmia requiring anti-arrhythmic (excluding beta blockers or digoxin)
Active coronary artery disease or ischaemia
Active clinically serious bacterial or fungal infections (> grade 2 National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3)
Known History of Human Immunodeficiency Virus (HIV) infection or chronic hepatitis B or C
Metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for 1 month prior to and following screening radiographic study)
Subjects with seizure disorders requiring medication (such as steroid or anti-epileptics)
History of organ allograft
Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
Known or suspected allergy to the investigational agent
Any condition that is unstable or which could jeopardize the safety of the subject and his/her compliance in the study. Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.

Excluded therapies include:

Anti-cancer chemotherapy, hormonal therapy or immunotherapy during the study or within 4 weeks of study entry. Mytomicin or nitroureas should not be given within 6 weeks of study entry
Significant surgery within 4 weeks prior to the start of study drug
Any bone marrow transplant or stem cell rescue within 4 months of the start of study drug
Radiotherapy during the study or within 3 weeks of the start of drug
Use of biologic response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CSF), within 3 weeks of study entry
Investigational drug therapy outside of this trial during or within 30 days prior to start of the study drug
Concomitant treatment with ketoconazole, itraconazole, ritonavir, or use of grapefruit juice
Prior use of Raf-Kinase Inhibitors (RKI), Methyl Ethyl Ketone (MEK) or farnesyl transferase inhibitors
Concomitant treatment or use of St. John's Wort
Prior use of bevacizumab and all other drugs that target Vascular Endothelial Growth Factor (VEGF)/VEGF receptors

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorafenib (Nexavar, BAY43-9006)	Sorafenib (Nexavar, BAY43-9006)	Sorafenib 400 mg administered twice daily (b.i.d.)

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Response (Complete or Partial)	Until 30 days after termination of active therapy	Number of subjects with metastatic breast cancer treated with single agent BAY43-9006 who had best overall response assessed as complete response (CR) or partial response (PR) as per Modified World Health Organization (WHO) Tumor Response Criteria.

Secondary Outcome Measures

Name	Time	Method
Overall Response Duration	Time from PR or CR to progression	Overall response duration was defined only for subjects achieving confirmed objective response (PR or CR). It was measured from start of treatment to the date when progressive disease was first objectively documented.
Survival Time	Start of treatment to death	After the end of treatment visit (30 days after the last dose), the subjects were monitored every 3 months for survival (visits/phone calls).
Time to Objective Response	Until objective response occurs	Defined only for subjects achieving objective tumor response from start of treatment to the date when confirmed PR or CR was first documented according to the Modified WHO Tumor Response Criteria.
Number of Subjects With Stable Disease up to Cycle 4	Until 30 days after termination of active therapy	Number of subjects who had not responded to treatment but had stable disease up to cycle 4.
Time to Progression	Until progression occurs	Time from start of treatment until progression was first documented.