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

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
chemotherapy	oxaliplatin, capecitabine, trastuzumab	-

Primary Outcome Measures

Name	Time	Method
Response Rate	up to 24 months from baseline	Number of patients with complete or partial response in the liver (RECIST version 1.1). Only patients with measurable disease are included in the protocol. Response rate number of patients with CR + PR divided with total number. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions,

Secondary Outcome Measures

Name	Time	Method
Survival	up to 7 years	All patients in intent-to-treat population , calculated from start of treatment to death of any course
PFS	up to 6 years	From start of therapy to progression or death of any cause.
Number of Patients Suitable for Local Therapy (Radiofrequency)	upon completion of treatment, an average of 7 months	Total number of patients receiving RF treatment or surgical treatment
Adverse Events	from start of treatment to 28 days after last treatment, an average of 7 months	Number of participants with at least 1 AE related to study treatment - The details on which AEs occured are listed in the Adverse Event section below