Capecitabine + Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer

Capecitabine in Combination With Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer, a Phase II Trial

Patients with pretreated, Her2-negative, advanced breast cancer will receive chemotherapy with capecitabine and bendamustine for a maximum of eight cycles and afterwards capecitabine alone until disease progression or unacceptable toxic effects. Safety assessments will be conducted in 3-weekly intervals, efficacy assessments (CT or MRI) will be conducted every 9 weeks.

Aim of this study is to determine whether treatment with capecitabine in combination with bendamustine is efficacious and safe.

40 eligible patients will be enrolled. A two-stage design efficacy and safety of bendamustine and capecitabine will be evaluated following recruitment of the first 20 patients. Upon favorable results a further 20 patients will be recruited to reach the target population of 40 evaluable patients.

Pretreatment for eligible patients must include anthracyclines and/or taxanes.

Inclusion Criteria:

• Signed informed consent

• Female patients, age ≥ 18 years (women of childbearing potential must have a negative pregnancy test at screening and must use effective contraception)

• Advanced or metastatic Her2-negative breast cancer, histologically confirmed

• At least one measurable lesion according to RECIST criteria (Version 1.1)

• Documented disease progression

• Patients with progression after anthracycline and/or taxane treatment(palliative or adjuvant)

• Life expectancy of at least 12 weeks

• Performance status 0-2

• Hematologic:

  • ANC (absolute neutrophil count) ≥ 1.5 x 109/L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100 x 109/L

• Liver Function:

  • Albumin ≥ 2.5 g/dL

  • Serum bilirubin ≤ 2 mg/dL

  • AST (Aspartate aminotransferase) and ALT (Alanine aminotransferase) ≤ 3 x ULN (Upper limit of Normal) without liver metastases

    • 5 x ULN if documented liver metastases

• Renal Function:

• Serum Creatinine ≤ 1.5 mg/dL OR Calculated Creatinine Clearance ≥ 40 mL/min

Exclusion Criteria:

• Pregnant or lactating women
• Serious medical or psychiatric disorders that would interfere with the patient's safety or informed consent
• Radiation of the target lesion within the last 4 weeks
• Active bacterial, viral or fungal infection
• Patients with clinically apparent brain metastases
• Known Positivity for HIV
• Positivity for Hepatitis B or C
• History of other malignancy; patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• Concurrent cancer therapy (chemotherapy, immunotherapy, antihormonal or biologic therapy) or concurrent treatment with an investigational drug
• Antihormonal therapy must have been discontinued prior to start of treatment (if possible at least 3 weeks before)
• Known hypersensitivity to the study drugs capecitabine and bendamustine or their excipients
• Pretreatment with capecitabine (pretreatment with infusional 5-FU (Fluorouracil) in the adjuvant or neoadjuvant setting is allowed) or bendamustine
• Treatment with sorivudine or derivates e.g. brivudin (Mevir©) within the last 4 weeks before and during study treatment with capecitabine