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Phase I/II Vinorelbine and Sorafenib as Salvage Therapy in Metastatic Breast Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase I/II Vinorelbine and Sorafenib as Salvage Therapy in Metastatic Breast Cancer



- To determine the safety, tolerability, and recommended phase II dose of sorafenib
tosylate when administered in combination with vinorelbine ditartrate in women with
stage IV adenocarcinoma of the breast. (Phase I)

- To evaluate the 4-month progression-free survival rate in patients treated with this
regimen at the maximum tolerated dose. (Phase II)


- To determine time to treatment failure in these patients.

- To determine the response rate in these patients.

- To determine the overall survival and progression-free survival of these patients.

- To evaluate the toxicity profile of this regimen.

OUTLINE: This is a phase I, dose-escalation study of sorafenib tosylate followed by a phase
II study.

Patients receive oral sorafenib tosylate on days 1-28 and vinorelbine ditartrate IV on days
1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed stage IV adenocarcinoma
of the breast; (unless metastatic disease is documented by computed tomography [CT]
scan, magnetic resonance imaging [MRI], or bone scan; also, skin disease that has not
been biopsied maybe used if in the investigators clinical opinion this represents
metastatic disease)

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan

- Prior adjuvant therapy, and up to 2 lines of prior chemotherapy (including
trastuzumab containing regimens in Her-2 positive patients) for metastatic disease
are allowed; prior radiation therapy is allowed, prior hormonal therapy is allowed;
the total number of patients enrolled with prior trastuzumab containing regimens will
not exceed 10; no more than 50% of enrolled patients will receive the study regimen
in a third line setting

- Life expectancy of greater than 6 months

- Performance status: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

- Hemoglobin >= 9.0 g/dl

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Total bilirubin =< 1.5 times ULN

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times the
upper limit of normal (ULN) (=< 5 x ULN for patients with liver involvement)

- Creatinine =< 1.5 times ULN

- International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial
thromboplastin time (PTT) 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
and monitored at least weekly, or as defined by the local standard of care, until INR
is stable

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; women of childbearing potential must have a
negative serum pregnancy test performed within 7 days to the start of treatment;
should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks prior;
patients who had bevacizumab within 4 weeks prior to entering the study are allowed

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases are excluded from this clinical trial; patients
with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2),
symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction
within the past 6 months, cardiac ventricular arrhythmias requiring anti-arrhythmic
therapy, or psychiatric illness/social situations that would limit compliance with
study requirements

- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months

- 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 dose of
study drug

- Serious non-healing wound, ulcer, or bone fracture

- Evidence or history of bleeding diathesis or coagulopathy

- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
study drug

- Use of St. John's Wort or rifampin (rifampicin)

- Known or suspected allergy to sorafenib or any agent given in the course of this

- Pregnant women

- Human immunodeficiency virus (HIV)-positive patients

- Any condition that impairs patient's ability to swallow whole pills

- Any malabsorption problem

- Patients who received prior sunitinib are excluded

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability

Outcome Time Frame:

28 days following the last course of treatment

Safety Issue:


Principal Investigator

Thehang H. Luu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

November 2008

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms



City of Hope Medical CenterDuarte, California  91010
South Pasadena Cancer CenterSouth Pasadena, California  91030