Advanced Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
Breast Cancer, investigational drug, drug therapy, Antineoplastic Protocols, Immunotherapy, Metastatic breast cancer, Advanced breast cancer, Stage IV breast cancer, Her-2/neu expressing breast cancer, Her-2/neu, Trastuzumab refractory
Brief summary
This study has the purpose to demonstrate clinical efficacy of the investigational new drug ertumaxomab in patients with human epidermal growth factor receptor-2 (HER-2/neu) overexpressing (3+ or 2+ with a positive Fluorescence In Situ Hybridization (FISH) test result) metastatic breast cancer progressing after trastuzumab treatment. Ertumaxomab is a trifunctional bispecific antibody targeting Her-2/neu on tumor cells and CD3 on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory immune effector cells (e.g. macrophages, dendritic cells \[DCs\] and natural killer \[NK\] cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these immune cells, which can trigger a complex anti-tumor immune response.
Detailed description
This study is an open-label, non-randomized, uncontrolled, two-stage phase II study evaluating the efficacy and safety of ertumaxomab. Ertumaxomab will be administered three times at 7 day intervals by constant rate 3 hour intravenous (i.v.) infusions according to the following dose schedule: 10 µg (day 0); 100 µg (day 7 ± 1 day) and 100 µg (day 14 ± 1 day) (flat doses).
Interventions
DRUGertumaxomab
Ertumaxomab will be intravenously administered to see if it can increase the patient's objective response rate.
Sponsors
Fresenius Biotech North America
Neovii Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Women ≥ 18 years, Negative pregnancy test at screening and life expectancy of at least 3 months * metastatic (stage IV) and not curable adenocarcinoma of the breast * Measurable disease, defined as at least one lesion that is measurable in one dimension (RECIST) * HER-2 overexpression 3+ or 2+ FISH positive * Patients must have received one prior therapy with trastuzumab as last treatment before entry into the study. If trastuzumab was given as single agent treatment, patients must have received prior chemotherapy for metastatic disease * Trastuzumab has been discontinued before study entry * disease had progressed during or after trastuzumab therapy * Eastern Cooperative Oncology Group (ECOG)performance score of ≤ 2 * Adequate hematological, liver and kidney function Key
Exclusion criteria
* Women who are pregnant or breast feeding * Any history or symptoms indicative of brain or central nervous system metastases * Prior diagnosis of any malignancy not cured by surgery alone less than 5 years before study entry (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) * Human anti-murine antibody positive or hypersensitivity to murine proteins and any other component of the study drug * Known autoimmune diseases, Human immunodeficiency virus (HIV), hepatitis B or C infection as well as other acute or chronic infection or other concurrent non-malignant co-morbidities that are uncontrolled * Any concurrent chemotherapy, hormonal therapy, immunotherapy or corticoid therapy * Concurrent antibiotic treatment * Any concurrent investigational treatment for metastatic disease Cardiovascular
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study) | patients are monitored for 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | patients are monitored for 6 months | The study was prematurely terminated, therefore no participants were analyzed |
| Clinical Benefit Rate | patients are monitored for 6 months | The study was prematurely terminated, therefore no participants were analyzed |
Countries
Canada, United States
Participant flow
Recruitment details
Open-label phase 2 study evaluating the efficacy and safety of ertumaxomab for the treatment of metastatic breast cancer tumors. Ertumaxomab will be administered 3 times at 7 day intervals by constant rate 3 hour intravenous (IV) infusions according to the following dose schedule: 10 µg (day 0); 100 µg (day 7±1)and 100 µg(day14±1)(flat doses).
Pre-assignment details
Patients were required to complete screening procedures and up to five treatment visits.
Participants by arm
| Arm | Count |
|---|---|
| Ertumaxomab | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Due to disease progression | 16 |
Baseline characteristics
| Characteristic | Ertumaxomab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Region of Enrollment Canada | 7 participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 11 / 19 |
Outcome results
Primary
Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)
Time frame: patients are monitored for 6 months
Population: The study was prematurely terminated, therefore no participants were analyzed. The primary endpoint was the objective response rate (ORR) to ertumaxomab (best response during the course of the study), defined as the number of patients with CR or PR according to RECIST, relative to the total population of treated patients
Secondary
Clinical Benefit Rate
The study was prematurely terminated, therefore no participants were analyzed
Time frame: patients are monitored for 6 months
Population: The study was prematurely terminated, therefore no participants were analyzed
Secondary
Duration of Response
The study was prematurely terminated, therefore no participants were analyzed
Time frame: patients are monitored for 6 months
Population: The study was prematurely terminated, therefore no participants were analyzed