This Phase I study will investigate the safety of BIBW 2992 in combination with standard dose pemetrexed (500mg/m2) given on a 21 day cycle in patients with advanced solid cancers. BIBW 2992 will be given on two different dose schedules; dosing on days 1-21 and dosing on days 1 to 6 of a 21 day cycle. The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), including BIBW 2992 have demonstrated efficacy in solid tumors including non-small cell lung cancer (NSCLC). In addition, pemetrexed has demonstrated efficacy and has been approved as single agent chemotherapy in second-line NSCLC patients with adenocarcinoma. The data obtained from this trial shall allow for a conclusion as to whether BIBW 2992 may be safely administered in advanced cancer patients in combination therapy with pemetrexed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
patient receives low dose BIBW 2992 po daily on day 1 of 21 day cycle
patient receives high dose BIBW 2992 po daily on day 1 of 21 day cycle
given intravenously on day 1 of a 21 day cycle
given intravenously on day 1 of a 21 day cycle
patient receives high dose BIBW 2992 po daily on days 1-6 on 1 of 21 day cycle
given intravenously on day 1 of a 21 day cycle
given intravenously on day 1 of a 21 day cycle
given intravenously on day 1 of a 21 day cycle
given intravenously on day 1 of a 21 day cycle
patient receives low dose BIBW 2992 po daily on days 1-6 on day 1 of 21 day cycle
patient receives medium dose BIBW 2992 po daily on day1 to 6 of a 21 day cycle
patient receives medium dose BIBW 2992 po daily on day 1 of 21 day cycle
1200.92.1001 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
1200.92.1002 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set
Occurence of DLT during the first course of treatment to determine the maximum tolerated dose (MTD) of Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).
Time frame: DLT were assessed during the first cycle (days 1-21)
Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set
Occurence of DLT during all courses of treatment with Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).
Time frame: DLT were assessed during all cycles of treatment
Objective Response (OR)
Objective Response is defined as complete response or partial response according to the response evaluation criteria in solid tumours (RECIST) version 1.1. Complete Response (CR): disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR): at least 30% decrease of the sum of longest diameter (LD) of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions together with an absolute increase in the sum of LD of at least 5 millimeters; Stable Disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD.
Time frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
Disease Control
Disease Control is defined as complete response, partial response, or stable disease according to the response evaluation criteria in solid tumours (RECIST) version 1.1.
Time frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
Progression Free Survival (PFS)
PFS was defined as the time from the first treatment to the occurence of tumour progression or death, whichever came first. It was assessed according to RECIST version 1.1 criteria.
Time frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
Tumour Shrinkage
Tumour shrinkage is defined as the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions.
Time frame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
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