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Randomised Phase II Study of Paclitaxel Alone Versus Paclitaxel Plus Sorafenib in Second- or Third-line Treatment of Patients With Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Metastatic Breast Cancer

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Trial Information

Randomised Phase II Study of Paclitaxel Alone Versus Paclitaxel Plus Sorafenib in Second- or Third-line Treatment of Patients With Metastatic Breast Cancer

Today breast carcinoma is the leading cancer type and the second frequent cause of cancer
death in adult women. This tumor remains a challenge in modern oncology despite recent
advances by introducing new classes of chemotherapy like taxanes and antibodies for the
HER-2/neu positive tumors. Recently it was shown that the combination of conventional
chemotherapy with a monoclonal antibody against VEGF can further increase the response and
progression free survival by combination with an antiangiogenic therapy. It is supposed that
this effect might result in a prolonged survival.

Sorafenib, a new developed oral inhibitor for tyrosine kinases which are responsible for the
signal transduction after binding to the VEGF receptor and the RAS-Raf-MEK-ERK pathway seems
efficient in the treatment of a broad range of tumors.

The multi-kinase inhibitor Sorafenib targets the Raf/MEK/ERK pathway at the level of Raf
kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β, thereby affecting both, the
tumour and the vasculature. Preclinical studies as well as phase I trials showed anti-tumour
activity in patients with metastatic breast cancer treated with single-agent sorafenib.

This multicentre, phase II, open-label, randomised study is designed to assess the potential
prolongation in progression free survival in patients with metastatic breast cancer in
combination with standard chemotherapy paclitaxel compared with the paclitaxel monotherapy.

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the breast

2. HER-2/neu negative (primary tumour site HER-2/neu negative by ICH/FISH test)

3. Second till third-line of chemotherapy

4. Female, age ≥ 18 years.

5. ECOG Performance Status of 0 or 1 (Karnofsky-Index ≥ 70%)

6. Life expectancy of at least 12 weeks.

7. Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion.
Lesions must be measured by Xray (pulmonary lesions only) or CT-scan or MRI (Patients
with only measurable bone lesions can be also included, as long they meet the
criteria for RECIST 1.1.; means, lytic bone lesions or mixed lytic-blastic bone
lesions with identifiable soft tissue components.)

8. No prior therapy for locally recurrent or metastatic disease with TKI's (RAS/Raf,
MEK, AKT), mTOR inhibitors and angiogenesis inhibitors (VEGV/VEGFR, PDGF/PDGFR) but
bevacizumab will be allowed.

9. Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:

- Hemoglobin ≥ 9.0 g/dl

- Absolute neutrophil count (ANC) ≥ 1,500/mm3

- Platelet count ≥ 100,000/μl

- Total bilirubin ≤ 1.5 x upper limit of normal

- ALT and AST ≤ 2.5 x upper limit of normal (< 5 x upper limit of normal for
patients with liver involvement of their cancer)

- Alkaline phosphatase ≤ 4 x upper limit of normal

- PT-INR and PTT ≤ 1.5 x upper limit of normal [Patients who are being
therapeutically anticoagulated with an agent such as coumadin or heparin will be
allowed to participate provided that no prior evidence of underlying abnormality
in these parameters exists.]

- Serum creatinine ≤ 1.5 x upper limit of normal.

10. Signed and dated informed consent before the start of specific protocol procedures.

Exclusion Criteria:

1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI
more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring
anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled

2. Known history of HIV infection or chronic hepatitis B or C

3. Active clinically serious infections (> grade 2 NCI-CTC version 4.02)

4. Prior clinical or radiological evidence of CNS metastases including previously
treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by
contrast enhanced head CT scan or MRI

5. Patients with seizure disorder requiring medication (such as steroids or

6. History of organ allograft

7. Patients with evidence or history of bleeding diathesis

8. Patients undergoing renal dialysis

9. Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumours [Ta, Tis & T1] or any cancer curatively
treated > 3 years prior to study entry.

10. Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment. Women
enrolled in this trial must use adequate barrier birth control measures during the
course of the trial.

11. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results

12. Any condition that is unstable or could jeopardise the safety of the patient and
their compliance in the study

13. Patients unable to swallow oral medications.

14. Patients with intolerance to Paclitaxel.

Excluded therapies and medications, previous and concomitant:

1. Anticancer chemotherapy, hormonotherapy or immunotherapy during the study or within 3
weeks of study entry.

2. Radiotherapy within 3 weeks of start of study drug, palliative radiotherapy will be

3. Major surgery within 4 weeks of start of study

4. Autologous bone marrow transplant or stem cell rescue within 4 months of study entry

5. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.
[G-CSF and other hematopoietic growth factors may be used in the management of acute
toxicity such as febrile neutropenia when clinically indicated or at the discretion
of the investigator; however they may not be substituted for a required dose
reduction.] [Patients taking chronic erythropoietin are permitted provided no dose
adjustment is undertaken within 2 months prior to the study or during the study]

6. Investigational drug therapy outside of this trial during or within 4 weeks of study

7. Previous treatment with paclitaxel within 1.line and 2.line palliative therapy
(Paclitaxel within (neo-) adjuvant therapy is allowed)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival (PFS)

Outcome Description:

The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer. Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death.

Outcome Time Frame:

app. 3 yrs

Safety Issue:


Principal Investigator

Friedrich Overkamp, Dr. med.

Investigator Role:

Principal Investigator


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

July 2010

Completion Date:

August 2014

Related Keywords:

  • Metastatic Breast Cancer
  • progression free survival
  • paclitaxel
  • sorafenib
  • metastatic breast cancer
  • Breast Neoplasms