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

Study Overview
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Brief Summary
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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.

Official Title
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Intra-hepatic Chemotherapy With Oxaliplatin Every Second Week in Combination With Systemic Capecitabine in Patient With Non-resectable Liver Metastases From Breast Cancer A Phase II Trial in Patients With Limited Extrahepatic Disease

Conditions
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Metastatic Breast Cancer, Liver Metastases

Intervention / Treatment
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* Drug: oxaliplatin, capecitabine, trastuzumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy<br> | Drug: oxaliplatin, capecitabine, trastuzumab<br>* Oxaliplatin intrahepatic capecitabine and trastuzumab systemic<br>* Other names: HAI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | 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, | up to 24 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Suitable for Local Therapy (Radiofrequency) | Total number of patients receiving RF treatment or surgical treatment | upon completion of treatment, an average of 7 months | 
| Survival | All patients in intent-to-treat population , calculated from start of treatment to death of any course | up to 7 years | 
| Adverse Events | 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 | from start of treatment to 28 days after last treatment, an average of 7 months | 
| PFS | From start of therapy to progression or death of any cause. | up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, liver metastases, intrahepatic chemotherapy