A Phase I Open Label Dose Escalation Study of Continuous Once-daily Oral Treatment With BIBW 2992 in Patients With Advanced Solid Tumors

Boehringer Ingelheim0 sites30 target enrollmentNovember 2004

ConditionsNeoplasms

InterventionsBIBW 2992

Overview

Investigation of maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamic parameters, and efficacy of BIBW 2992

Registry

clinicaltrials.gov

Start Date

November 2004

End Date

September 2006

Last Updated

11 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Sponsor

Responsible Party

Sponsor

•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)

•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)

dose escalation

Intervention: BIBW 2992

Maximum tolerated dose (MTD) of BIBW 2992

Time Frame: up to 168 days

Incidence and intensity of Adverse Events according to Common Terminology Criteria (CTC version 3)

Time Frame: up to 23 months

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)
Area under the plasma concentration-time curve (AUC) for several time points(up to 28 days)
Predose plasma concentration(Predose on day 8, 15, 22 and 27)
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)
Mean residence time after oral administration at steady state (MRTpo,ss)(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)