A Phase I Open Label Dose Escalation Study of Once-daily Oral Treatment With BIBW 2992 for 28 Days in Patients With Advanced Solid Tumours

Boehringer Ingelheim0 sites53 target enrollmentNovember 2004

ConditionsNeoplasms

InterventionsBIBW 2992

DrugsBIBW 2992

Overview

Phase: Phase 1
Intervention: BIBW 2992
Conditions: Neoplasms
Sponsor: Boehringer Ingelheim
Enrollment: 53
Primary Endpoint: Maximum tolerated dose (MTD) of BIBW 2992
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The primary objective of the study was to identify the maximum tolerated dose and to evaluate safety, pharmacokinetics, pharmacodynamic parameters, and efficacy of BIBW 2992.

Registry

clinicaltrials.gov

Start Date

November 2004

End Date

March 2007

Last Updated

11 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female patients with confirmed diagnosis of advanced, non-resectable and / or metastatic solid tumours, of types historically known to express EGFR and/or HER2, 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 completely 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 tumour deposits (RECIST) by one or more techniques (X-ray, CT, MRI) and/or recognized tumour markers such as prostate-specific antigen prostate cancer) or cancer antigen 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, Système Internationale (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, SI unit equivalent)

Arms & Interventions

BIBW 2992

dose escalation

Intervention: BIBW 2992

BIBW 2992, fasted

food effect part: maximum tolerated dose of BIBW 2992

Intervention: BIBW 2992

BIBW 2992, fed

food effect part: maximum tolerated dose of BIBW 2992

Intervention: BIBW 2992

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD) of BIBW 2992

Time Frame: up to 24 weeks

Incidence and intensity of Adverse Events according to Common Toxicity Criteria (CTC version 3) associated with increasing doses of BIBW 2992

Time Frame: up to 28 weeks

Secondary Outcomes

mean residence time after oral administration (MRTpo(ss))(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
apparent clearance (CL/F(ss))(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
apparent volume of distribution during the terminal phase (Vz/F(ss))(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
Accumulation ratio between Day 1 and Day 27 with respect to Cmax (RA1) and AUC (RA2)(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
Modulation of biomarker (EGFR, p-EGFR, p-MAPK, p-Akt, Ki 67, p-27KIP1) in skin biopsies(Baseline and day 28 of the first treatment period)
Modulation of biomarker (EGFR, p-EGFR, HER2 (Class I Tyrosine Kinase Receptor), p-MAPK (mitogen-activated protein kinase), p-Akt, Ki 67, p-27KIP1) in tumour biopsies in six or more patients treated at the MTD(Baseline and day 28 of the first treatment period)
Objective tumour response(up to 25 weeks)
Correlation of EGFR, HER2, estrogen receptor (ER) and progesterone receptor (PrR) immunohistochemical status as based on tumour biopsies, or excisions obtained prior to this study, with objective tumour responses(up to 25 weeks)
Area under the plasma concentration-time curve (AUC) for several time points(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
Percentage of AUC0-∞ that is obtained by extrapolation (%AUCtz-∞)(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
predose plasma concentration(predose on days 8, 15, 22 and 27)
Plasma concentration(24 hours after drug administration on the first (C24,1) and the Day 27 dose (C24,27))
Maximum measured plasma concentration (Cmax) for several time points(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
Time from dosing to the maximum plasma concentration (tmax) for several time points(up to 648 hours after first drug administration, pre-dose on day 15 and 28)
terminal half-life (t1/2(ss))(up to 648 hours after first drug administration, pre-dose on day 15 and 28)