Breast Neoplasms
Conditions
Brief summary
maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of bivatuzumab mertansine
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. female patients aged 18 years or older 2. patients with breast cancer positive for CD44v6 in at least 50 % of the tumour cells 3. patients with local and / or regional recurrent disease or distant metastases who are refractory to anthracyclines and / or taxanes (unless contraindications to taxanes and / or anthracyclines) or not amenable to established treatments 4. measurable tumour deposits by one or more radiological techniques (MRI, CT) 5. life expectancy of at least 6 months 6. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 7. patients must have given written informed consent (which must be consistent with International Conference of Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation)
Exclusion criteria
1. hypersensitivity to humanised or murine antibodies, immunoconjugates or the excipients of the trial drugs 2. known secondary malignancy requiring therapy 3. active infectious disease 4. brain metastases requiring therapy 5. neuropathy grade 2 or above 6. absolute neutrophil count less than 1,500/mm3 7. platelet count less than 100,000/mm3 8. bilirubin greater than 1.5 mg/dl (\> 26 μmol/L, système internationale (SI) unit equivalent) 9. aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 3 times the upper limit of normal 10. serum creatinine greater than 1.5 mg/dl (\> 132 μmol/L, SI unit equivalent) 11. concomitant non-oncological diseases which are considered relevant for the evaluation of the safety of the trial drug 12. chemo- or immunotherapy within the past four weeks prior to treatment with the trial drug or during the trial (except for present trial drug) 13. radiotherapy to breast and thorax region within the past four weeks prior to treatment with the trial drug or during the trial 14. women who are sexually active and unwilling to use a medically acceptable method of contraception 15. pregnancy or lactation 16. treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug) 17. patients unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) | up to 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of distribution during the terminal elimination phase (Vz) | up to 14 days after last drug administration | — |
| Incidence of adverse events | up to 14 days after last drug administration | graded according to common toxicity criteria (CTC) |
| Number of patients with clinically significant findings in laboratory examinations | up to 14 days after last drug administration | — |
| Number of patients with clinically significant findings in vital signs | up to 14 days after last drug administration | — |
| Number of patients with development of Human Anti-Human Antibody (HAHA) | up to 14 days after last drug administration | — |
| Area under the serum concentration time curve from time zero to time point 168 hours (AUC0-168) | up to 168 hours | — |
| Area under the serum concentration time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) | up to 14 days after last drug administration | — |
| Area under the serum concentration time curve from time point zero to infinity (AUC0-∞) | up to 14 days after last drug administration | — |
| Maximum serum concentration (Cmax) | up to 14 days after last drug administration | — |
| Volume of distribution at steady state (Vss) | up to 14 days after last drug administration | — |
| Terminal elimination half-life (t1/2) | up to 14 days after last drug administration | — |
| Mean residence time (MRT) | up to 14 days after last drug administration | — |
| Total body clearance (CL) | up to 14 days after last drug administration | — |
| Trough concentration at steady state (Cpre,ss) | up to 7 days after drug administration | — |
| Minimum serum concentration during the dosing interval τ at steady state (Cmin,ss) | up to 7 days after drug administration | — |
| Linearity index (LI) | up to 14 days after last drug administration | — |
| Accumulation factor (RA) | up to 14 days after last drug administration | — |
| Tumor response | up to 14 days after last drug administration | according to response evaluation criteria in solid tumours (RECIST) |
| Time to reach maximum serum concentration (tmax) | up to 14 days after last drug administration | — |
Outcome results
None listed