1st or 2nd Line MBC (Metastatic Breast Cancer) With Previous Avastin (Bevacizumab) Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Gemcitabine; Sorafenib; Placebo; Capecitabine
Intervention description: Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours); Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours); Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine).
Intervention MeSH terms: Gemcitabine; Capecitabine; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

Summary:

      The study is being conducted to compare progression-free survival in patients treated with
      sorafenib and gemcitabine/capecitabine versus patients treated with placebo and
      gemcitabine/capecitabine for locally advanced or metastatic breast cancer that has progressed
      during or following treatment with a bevacizumab-containing regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the breast.

          -  Measurable or evaluable locally advanced or metastatic disease.

          -  Age ≥18 years.

          -  Disease progression during or after treatment with a bevacizumab-containing regimen in
             the adjuvant or first-line metastatic setting.

          -  Patients must have discontinued chemotherapy at least 3 weeks prior to randomization.

          -  No more than one prior chemotherapy regimen for locally advanced or metastatic
             disease.

          -  Prior hormonal therapy allowed provided it has been discontinued prior to
             randomization.

          -  Prior radiation therapy is allowed but must be completed at least 3 weeks prior to
             randomization. Previously radiated area(s) must not be the only site of disease.

          -  ECOG Performance Status of 0 or 1.

          -  Adequate bone marrow, liver, and renal function

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to randomization, and must agree to use adequate contraception
             prior to study entry, for the duration of study participation and 28 days after the
             last study drug dosing.

          -  Patients must be able and willing to sign a written informed consent.

          -  Patients must be able to swallow and retain oral medication.

        Exclusion Criteria:

          -  Patients with breast cancer over-expressing human epidermal growth factor receptor 2
             (HER-2) (gene amplification by FISH or 3+ over-expression by immunohistochemistry).
             Patients with unknown HER-2 status are not eligible.

          -  Patients with active brain metastases.

          -  Major surgery, open biopsy, or significant traumatic injury within 4 weeks of
             randomization.

          -  Prior use of gemcitabine/capecitabine or sorafenib.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  Substance abuse, or medical, psychological, or social condition that may interfere
             with the patient's participation in the study or evaluation of the study results.

          -  Use of cytochrome P450 enzyme-inducing anti-epileptic drugs is not allowed.

          -  Clinically significant cardiac disease

          -  Uncontrolled hypertension

          -  Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident
             including transient ischemic attacks within the past 6 months.

          -  Pulmonary hemorrhage/bleeding event > NCI-CTCAE Grade 2 within 4 weeks of
             randomization.

          -  Any other hemorrhage/bleeding event ≥ NCI-CTCAE Grade 3 within 4 weeks of
             randomization.

          -  Active clinically serious infection > NCI-CTCAE Grade 2.

          -  Known HIV infection or chronic hepatitis B or C (the safety and effectiveness of
             sorafenib in this patient population have not been studied).

          -  Previous or concurrent cancer that is distinct in primary site or histology from
             breast cancer EXCEPT cervical cancer in-situ, treated basal cell carcinoma,
             superficial bladder tumors [Ta and Tis] or any cancer curatively treated > 5 years
             prior to randomization.

          -  Known or suspected allergy to sorafenib or gemcitabine/capecitabine.

          -  Prior or concurrent use of St. John's Wort or rifampin (rifampicin) within 3 weeks of
             randomization.

          -  Concurrent anti-cancer therapy other than gemcitabine/capecitabine and
             sorafenib/placebo.

          -  Prior treatment with any agent that targets VEGF or VEGFR (licensed or
             investigational), except bevacizumab.

          -  Women who are pregnant or breast-feeding.

          -  Use of any investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding randomization.

          -  Inability to comply with protocol and/or not willing or not available for follow-up
             assessments.

          -  Any condition which in the investigator's opinion makes the patient unsuitable for the
             study participation.