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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer; Liver Metastases
• Intervention / Treatment: Drug: oxaliplatin, capecitabine, trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, DK-2730
    • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chemotherapy	Drug: oxaliplatin, capecitabine, trastuzumab; Oxaliplatin intrahepatic capecitabine and trastuzumab systemic; Other Names: HAI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dorte Nielsen
• Investigators: Principal Investigator: Dorte Nielsen, Professor, Professor

Publications and helpful links

General Publications

• Lindgaard SC, Brinch CM, Jensen BK, Norgaard HH, Hermann KL, Theile S, Larsen FO, Jensen BV, Michelsen H, Nelausen KM, Holm VH, Ekblad L, Soerensen PG, Nielsen DL. Hepatic arterial therapy with oxaliplatin and systemic capecitabine for patients with liver metastases from breast cancer. Breast. 2019 Feb;43:113-119. doi: 10.1016/j.breast.2018.12.002. Epub 2018 Dec 5.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 30, 2011
• First Posted (Estimated): July 4, 2011

Study Record Updates

• Last Update Posted (Actual): December 11, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; liver metastases; intrahepatic chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Breast Diseases; Liver Diseases; Neoplastic Processes; Breast Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Capecitabine; Oxaliplatin
• Other Study ID Numbers: MA 0918