Intra-hepatic Chemotherapy in Patients With Liver Metastases From Breast Cancer and Limited Extrahepatic Disease

• Number of patients suitable for local therapy (radiofrequency) [ Time Frame: 6 months after last patient included ] [ Designated as safety issue: No ]
  Total number of patients receiving RF treatment or surgical treatment
• Survival [ Time Frame: 6 months after last patient included ] [ Designated as safety issue: No ]
  All patients in intent-to-treat population , calculated from start of treatment to death of any course
• toxicity [ Time Frame: 28 days after last treatment of last patient ] [ Designated as safety issue: Yes ]
  All patients who received at least one dose of study drug are evaluable for toxicity. CTC version 3.0 will be used.
• PFS [ Time Frame: 6 months after last patient included ] [ Designated as safety issue: No ]
  From start of therapy to progression or death of any cause.

This is a phase II trial evaluating intra-hepatic chemotherapy with oxaliplatin every second week in combination with systemic capecitabine and in patients with a HER2-positive tumour in combination with trastuzumab (Herceptin®) in patient with non-resectable liver metastases from breast cancer.

Only patients with limited extrahepatic disease are included.

• Metastatic Breast Cancer
• Liver Metastases

Inclusion Criteria:• Informed consent

• Age > 18 years
• Performance status 0-1; expected survival ≥ 3 months
• Patient with histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the breast
• Liver metastases not suitable for local treatment
• Extrahepatic disease should be determined by PET-CT-scan.
• No progression on treatment with capecitabine.
• Prior treatment with taxane (adjuvant or for metastatic disease)
• Metastases < 70 % of the liver
• Neutrophile granulocytes > 1.5 x 109/l og thrombocytes > 100 x 109/l
• Bilirubin < 2.0 x UNL (upper normal limit).
• Creatinine-clearance > 30 ml/min.
• INR < 1.6.
• If the patient is HER2-positive:Baseline LVEF ≥ 50 %

Exclusion Criteria:

• History of chemotherapy within the 4-week period prior to the start of trial medication
• Other current or prior malignant disease except adequately treated and cured carcinoma in situ of the cervix or squamous cell carcinoma of the skin.
• Previous treatment with oxaliplatin
• Cytotoxic or experimental treatment within a 14 days period before start of trial medication
• The patient is not allowed to participate in other clinical trials.
• Any clinical symptoms suggesting peripheral neuropathy < or equal to grade 2 or CNS metastases (In case of clinical suspicion on CNS metastases a MR or CT scan should be performed within 4 weeks before inclusion
• Other severe medical conditions e.g. severe cardial disease or AMI < 1 year
• Presence of diseases which prevent oral therapy.
• Patients with uncontrolled infection
• Pregnant or lactating women
• Women capable of childbearing not using a sufficient non—hormonal method of birth control
• Patients not able to understand the treatment or to collaborate.
• Prior serious or unsuspected reaction after treatment with fluoropyrimidine
• Known prior hypersensitivity reactions to the agents

If the patient is HER2-positive:

• Dyspnoea in due to complication related to malignant disease e.g.lung metastases with lymphangitis or other conditions with need of supportive oxygen.

• Odense University Hospital
• Aarhus University Hospital