Liver Metastases, Metastatic Breast Cancer
Conditions
Keywords
breast cancer, liver metastases, intrahepatic chemotherapy
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.
Interventions
Oxaliplatin intrahepatic capecitabine and trastuzumab systemic
Sponsors
Dorte Nielsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Survival | up to 7 years | All patients in intent-to-treat population , calculated from start of treatment to death of any course |
| 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 |
| PFS | up to 6 years | From start of therapy to progression or death of any cause. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy oxaliplatin, capecitabine, trastuzumab: Oxaliplatin intrahepatic capecitabine and trastuzumab systemic | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | Chemotherapy | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 8 Participants | — |
| Age, Categorical Between 18 and 65 years | 30 Participants | — |
| Age, Continuous | 54.5 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Denmark | 38 participants | — |
| Sex: Female, Male Female | 38 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 33 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 8 / 38 |
Outcome results
Primary
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,
Time frame: up to 24 months from baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy | Response Rate | CR | 2 Participants |
| Chemotherapy | Response Rate | PR | 13 Participants |
| Chemotherapy | Response Rate | SD | 21 Participants |
| Chemotherapy | Response Rate | PD | 1 Participants |
| Chemotherapy | Response Rate | NE | 1 Participants |
Secondary
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
Time frame: from start of treatment to 28 days after last treatment, an average of 7 months
Population: All patients who received at least one dose of study drug are evaluable for toxicity. CTC version 3.0 will be used.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy | Adverse Events | 38 Participants |
Secondary
Number of Patients Suitable for Local Therapy (Radiofrequency)
Total number of patients receiving RF treatment or surgical treatment
Time frame: upon completion of treatment, an average of 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy | Number of Patients Suitable for Local Therapy (Radiofrequency) | 2 Participants |
Secondary
PFS
From start of therapy to progression or death of any cause.
Time frame: up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | PFS | 12.8 months |
Secondary
Survival
All patients in intent-to-treat population , calculated from start of treatment to death of any course
Time frame: up to 7 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Survival | 24.0 months |