BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours

Phase 1

Completed

Conditions: Neoplasms

Interventions: Drug: BIBW 2992 low dose
Drug: BIBW 2992 high dose 6 day
Drug: BIBW 2992 high dose
Drug: BIBW 2992 medium dose 6 day
Drug: BIBW 2992 medium dose
Drug: BIBW 2992 low dose 6 day
Drug: pemetrexed

Registration Number: NCT01169675

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 53

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIBW 2992 low dose	BIBW 2992 low dose	patient receives low dose tablet BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 medium dose 6 day	BIBW 2992 medium dose 6 day	patient receives medium BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 high dose 6 day	BIBW 2992 high dose 6 day	patient receives high dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 medium dose	BIBW 2992 medium dose	patient receives medium dose BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 high dose	BIBW 2992 high dose	patient receives high dose BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 low dose 6 day	BIBW 2992 low dose 6 day	patient receives low dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 low dose	pemetrexed	patient receives low dose tablet BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 medium dose	pemetrexed	patient receives medium dose BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 high dose	pemetrexed	patient receives high dose BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 low dose 6 day	pemetrexed	patient receives low dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 medium dose 6 day	pemetrexed	patient receives medium BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle
BIBW 2992 high dose 6 day	pemetrexed	patient receives high dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Primary Outcome Measures

Name	Time	Method
Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set	DLT were assessed during the first cycle (days 1-21)	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).

Secondary Outcome Measures

Name	Time	Method
Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set	DLT were assessed during all cycles of treatment	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).
Objective Response (OR)	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	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.
Disease Control	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	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.
Progression Free Survival (PFS)	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	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.
Tumour Shrinkage	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	Tumour shrinkage is defined as the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions.

Trial Locations

Locations (2): 1200.92.1001 Boehringer Ingelheim Investigational Site
🇨🇦
Edmonton, Alberta, Canada
1200.92.1002 Boehringer Ingelheim Investigational Site
🇨🇦
Hamilton, Ontario, Canada