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Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer



- To evaluate the efficacy of sorafenib tosylate and paclitaxel by measuring tumor
response, as defined by RECIST criteria, in patients with metastatic, HER2-negative
breast cancer.


- To evaluate time to disease progression in patients treated with this regimen.

- To evaluate six-month progression-free survival of patients treated with this regimen.

- To evaluate time to treatment failure in patients treated with this regimen.

- To evaluate clinical benefit rate (tumor response and stable disease) at 24 weeks in
patients treated with this regimen.

- To evaluate duration of response in patients treated with this regimen.

- To evaluate the tolerability of this regimen in these patients.

- To examine the relationship of gene expression and tissue/serum protein markers, where
available, related to response to therapy focusing on growth factor receptor pathways.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice daily on days 1-28 and paclitaxil IV over 1
hour on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks.

Inclusion Criteria


Inclusion criteria:

- Histologically* confirmed breast cancer

- Stage IV (metastatic) disease

- Radiographic evidence of metastases NOTE: *Histological confirmation of the
actual metastasis is not required.

- Measurable disease by RECIST criteria defined as ≥ 1 unidimensionally measurable
lesion ≥ 20 mm by conventional techniques (i.e., physical examination, CT scan, MRI,
or x-ray) or ≥ 10 mm by spiral CT scan

- No prior radiotherapy unless growth has been documented following radiotherapy

- Primary tumor or metastatic tumor HER2-negative, defined as the following:

- Immunohistochemistry of 0 or 1+ OR the equivalent, if an automated quantitative
assay is used

- HER2 fluorescent in situ hybridization (FISH) assay negative as defined by a
HER2:chromosome 17 centromeric probe ratio < 1.8 (or < 2.2 if
immunohistochemistry is less than 3+ or equivalent) OR equivalent values for
negative FISH assays that do not normalize to chromosome 17

- Hormone-receptor positive (estrogen receptor-[ER] or progesterone receptor
[PgR]-positive) disease or hormone receptor-negative (ER- or PgR-negative) disease

- Tumor block from initial breast cancer primary or a biopsy of a metastatic site must
be available for correlative studies

- Brain metastases allowed provided the patient is stable after completion of treatment
(i.e., surgery and/or radiotherapy), asymptomatic, and off steroids with 2
consecutive stable brain scans at least 4 weeks after radiotherapy

Exclusion criteria:

- Bone-only or other nonmeasurable-only disease

- Newly diagnosed brain metastases


Inclusion criteria:

- ECOG performance status 0-1

- Life expectancy > 6 months

- Menopausal status not specified

- WBC ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Total bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT transaminases ≤ 2.5 times ULN (< 5 times ULN if liver involvement)

- Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min

- INR < 1.5 OR PT/PTT normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to and during (women and men)
and for at least 3 months after (men) study therapy

- Able to swallow and absorb oral medications

Exclusion criteria:

- Active or uncontrolled medical illness (e.g., active infection > CTCAE grade 2),
including any of the following:

- HIV or chronic hepatitis B or C

- Uncontrolled diabetes

- NYHA class II-IV uncompensated congestive heart failure

- Unstable angina (anginal symptoms at rest)

- New onset angina (i.e., began within the past 3 months)

- Coronary artery disease

- Myocardial infarction within the past 6 months

- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- Evidence of bleeding diathesis or coagulopathy

- Pulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of first dose of
study drug

- Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first study

- Thrombotic or embolic events (i.e., cerebrovascular accident), including transient
ischemic attacks within the past 6 months

- Hypertension that cannot be controlled with medication to ≤ 150/90 mm Hg

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sorafenib tosylate

- Prior invasive cancer other than breast cancer except nonmelanoma skin cancer

- Chronic nonhealing wound or ulcer


- No more than 1 prior chemotherapy regimen for metastatic breast cancer (MBC)

- At least 3 weeks since prior hormonal therapy for MBC or adjuvant or neoadjuvant

- More than 1 year since adjuvant paclitaxel

- At least 4 weeks since major thoracic, abdominal, or pelvic surgery and recovered

- At least 3 weeks since prior and no concurrent investigational drugs

- Concurrent bisphosphonates allowed

- Concurrent anticoagulation agents (i.e., warfarin or heparin) allowed

- No anticipated need for or concurrent radiotherapy

- No concurrent Hypericum perforatum (St. John wort) or rifampin (rifampicin)

- No other concurrent anti-neoplastic drugs

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Safety Issue:


Principal Investigator

Barbara B. Haley, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Simmons Cancer Center



Study ID:




Start Date:

October 2007

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • male breast cancer
  • recurrent breast cancer
  • HER2-negative breast cancer
  • Breast Neoplasms



Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390