Neoplasms
Conditions
Brief summary
Investigation of maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamic parameters, and efficacy of BIBW 2992
Interventions
DRUGBIBW 2992
Sponsors
Boehringer Ingelheim
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
* Male or female patients with confirmed diagnosis of advanced, non-resectable and/or metastatic solid tumors, of types historically known to express EGFR and/or HER2 (Human Epidermal Growth Factor Receptor), who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment preferably patients with breast, colorectal or prostate cancer * Age 18 years or older * Life expectancy of at least three (3) months * Written informed consent that is consistent with International Conference on Harmonization - Good Clinical Practice guidelines * Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2 * Patients recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC \<=Grade 1 * Patients must be recovered from previous surgery The 12 additional patients recruited at the MTD must also meet the following criteria: * Measurable tumor deposits (RECIST) by one or more techniques (X-ray, CT, MRI) and/or recognized tumor markers such as prostate-specific antigen (PSA) (prostate cancer) or cancer antigen (CA) 125 (ovarian cancer)
Exclusion criteria
* Active infectious disease * Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea * Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol * Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least eight (8) weeks, no history of cerebral edema or bleeding in the past eight (8) weeks and no requirement for steroids or anti-epileptic therapy * Cardiac left ventricular function with resting ejection fraction CTC \>=Grade 1 * Absolute neutrophil count (ANC) less than 1500/mm3 * Platelet count less than 100 000/mm3 * Bilirubin greater than 1.5 mg /dl (\>26 μmol /L, SI unit equivalent) * Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal) * Serum creatinine greater than 1.5 mg/dl (\>132 μmol/L, Système Internationale unit equivalent) * Women and men who are sexually active and unwilling to use a medically acceptable method of contraception * Pregnancy or breast-feeding * Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy or hormone therapy (excluding Luteinizing Hormone-Releasing Hormone (LHRH) agonists, or other hormones taken for breast cancer, or bisphosphonates), or participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study * Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (eight weeks for trastuzumab) * Patients unable to comply with the protocol * Active alcohol or drug abuse A patient may be eligible for re-treatment after the previous course is finished. A patient will not be eligible if any of the following conditions are met: * Patients with clinical signs of disease progression or if latest X-ray, CT or MRI reveals disease progression * Cardiac left ventricular function CTC Grade ≥ 2 at any time during the previous course * Patients fulfilling any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) of BIBW 2992 | up to 168 days |
| Incidence and intensity of Adverse Events according to Common Terminology Criteria (CTC version 3) | up to 23 months |
Secondary
| Measure | Time frame |
|---|---|
| Plasma concentration at 24 h following the first (C24,1) and the Day 27 dose (C24,27) | 24 hours after drug administration on day 24 and 27 |
| Plasma concentration at 3 h following the first dose (C3,1) | 3 hours after the first dose on day 1 |
| Maximum measured plasma concentration at steady state on Day 27 (Cmax,ss) | up to 24 hours after drug administration on day 27 |
| Time from dosing to the maximum plasma concentration at steady state on Day 27 (tmax,ss) | up to 24 hours after drug administration on day 27 |
| Terminal half-life at steady state (t1/2,ss) | up to 28 days |
| Area under the plasma concentration-time curve (AUC) for several time points | up to 28 days |
| Apparent clearance at steady state (CL/F,ss) | up to 28 days |
| Apparent volume of distribution during the terminal phase at steady state (Vz/F,ss) | up to 28 days |
| Objective tumor responses | up to 23 months |
| Correlation of EGFR (epidermal growth factor receptor), HER2, estrogen receptor (ER) and progesterone receptor (PrR) immunohistochemical status as based on tumor biopsies, or excisions obtained prior to this trial, with objective tumor responses | up to 23 months |
| Mean residence time after oral administration at steady state (MRTpo,ss) | up to 28 days |
| Predose plasma concentration | Predose on day 8, 15, 22 and 27 |
Outcome results
None listed