Breast Cancer, Breast Neoplasms
Conditions
Keywords
Cancer
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.
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg administered twice daily (b.i.d.)
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | Until progression occurs | Time from start of treatment until progression was first documented. |
| 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. |
| 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). |
| 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. |
Countries
Germany, Italy
Participant flow
Recruitment details
Subjects were enrolled from 03 Feb 2004 to 29 Jul 2004 by 3 centers in Germany and 4 centers in Italy.
Pre-assignment details
2 subjects were excluded during screening phase: 1 withdrawal of consent and 1 protocol violation.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) Sorafenib 400 mg administered twice daily (b.i.d.) | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Survival Follow-Up | Alive | 7 |
Baseline characteristics
| Characteristic | Sorafenib (Nexavar, BAY43-9006) |
|---|---|
| Age Continuous | 55.4 years STANDARD_DEVIATION 10.8 |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 0: fully active | 30 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 1: Restricted strenous activity, ambulatory | 22 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 2: Ambulatory, difficulty in walking | 2 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 3: Limited self-care, partly confined to bed | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 4: Completely disabled, no self-care | 0 participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 0 Participants |
| Stage of disease at study entry (Tumor, Nodules, Metastasis (TNM) classification) Stage I | 0 participants |
| Stage of disease at study entry (Tumor, Nodules, Metastasis (TNM) classification) Stage II | 0 participants |
| Stage of disease at study entry (Tumor, Nodules, Metastasis (TNM) classification) Stage III | 0 participants |
| Stage of disease at study entry (Tumor, Nodules, Metastasis (TNM) classification) Stage IV -most advanced | 54 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 54 |
| serious Total, serious adverse events | 22 / 54 |
Outcome results
Primary
Number of Subjects With Response (Complete or Partial)
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.
Time frame: Until 30 days after termination of active therapy
Population: Intent to treat population consisted of subjects who received at least 1 dose of sorafenib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Number of Subjects With Response (Complete or Partial) | Complete response (CR) | 0 participants |
| Sorafenib (Nexavar, BAY43-9006) | Number of Subjects With Response (Complete or Partial) | Partial response (PR) | 1 participants |
| Sorafenib (Nexavar, BAY43-9006) | Number of Subjects With Response (Complete or Partial) | Stable disease (SD) | 20 participants |
| Sorafenib (Nexavar, BAY43-9006) | Number of Subjects With Response (Complete or Partial) | Progressive disease (PD) | 31 participants |
| Sorafenib (Nexavar, BAY43-9006) | Number of Subjects With Response (Complete or Partial) | Not evaluated | 2 participants |
Secondary
Number of Subjects With Stable Disease up to Cycle 4
Number of subjects who had not responded to treatment but had stable disease up to cycle 4.
Time frame: Until 30 days after termination of active therapy
Population: Intent to treat population consisting of subjects who received at least 1 dose of sorafenib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Number of Subjects With Stable Disease up to Cycle 4 | 12 participants |
Secondary
Overall Response Duration
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.
Time frame: Time from PR or CR to progression
Population: 1 subject out of 54 achieved PR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Overall Response Duration | 256 days |
Secondary
Survival Time
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 frame: Start of treatment to death
Population: Intent to treat population consisting of subjects who received at least 1 dose of sorafenib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Survival Time | 259 days |
Secondary
Time to Objective Response
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.
Time frame: Until objective response occurs
Population: 1 subject out of 54 achieved PR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Time to Objective Response | 145 days |
Secondary
Time to Progression
Time from start of treatment until progression was first documented.
Time frame: Until progression occurs
Population: Of the intent to treat population, 4 subjects died before assessment of progression; for 1 subject the progression date not available; and 1 subject was lost to follow-up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Time to Progression | 58 days |