To determine the maximum tolerated dose, safety, pharmacokinetics and anti-tumour efficacy of oral BIBW 2992 in combination with intravenous or oral vinorelbine
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Patients will receive 20mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.
Patients will receive 40mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.
Patients will receive 50mg dosage of BIBW 2992 plus standard dosage of vinorelbine.
1200.69.3301 Boehringer Ingelheim Investigational Site
Toulouse, France
1200.69.3302 Boehringer Ingelheim Investigational Site
Villejuif, France
Number of Participants With Dose-limiting Toxicities (DLT)
Number of participants with DLT for the determination of the Maximum Tolerated Dose (MTD). 3+3 dose escalation design. MTD based on DLTs during first treatment course. After MTD was determined, additional patients were included at the MTD in an expansion cohort.
Time frame: 28 days
Number of Patients With Best Overall Response
Overall response is defined as complete response, partial response and stable disease and was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST 1.0). Complete response (CR) and partial response (PR) had to be confirmed by a subsequent tumour assessment at least 28 days after the criteria for CR or PR were first met. To confirm a status of stable disease, the duration of stable disease was to be at least 42 days.
Time frame: From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Number of Patients With Objective Response (OR)
OR is defined as confirmed complete response and confirmed partial response (PR) and was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST 1.0).
Time frame: From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Number of Patients With Disease Control (DC)
DC is defined as confirmed complete response (CR), partial response (PR) and stable disease (SD) and was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST 1.0).
Time frame: From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
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Patients will receive 60 mg/m² Vinorelbine per os at J1 J8 and J15
Patients will receive 80 mg/m² Vinorelbine per os at J22
Patients will receive 25 mg/m² of Vinorelbine i.v.
Time to Objective Response
The time to OR was the duration from the first treatment to the time when the measurement criteria for first documented confirmed CR and/or PR were met according to RECIST 1.0 criteria.
Time frame: From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Duration of Objective Response
The duration of objective response was measured from the time of first documented confirmed CR or PR to the time of progressive disease or death, whichever occured earlier.
Time frame: From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Duration of Disease Control
Duration of disease control was measured from the start of study treatment to the time of progression or death, whichever occured first.
Time frame: From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Best Percentage Change in Tumour Size
Best percentage change in tumour size was the best percentage change in the sum of diameters of target lesions and was calculated as (minimum sum of diameters post baseline - sum of diameters at baseline)/sum of diameters at baseline. Negative values indicate a decrease, positive values an increase.
Time frame: Screening and every 8 weeks after starting of treatment, up to 44 weeks.
Progression-free Survival (PFS)
PFS was defined as the time from the first dose of study medication to the occurrence of tumour progression or death, whichever came first. It was assessed according to RECIST 1.0. Median time results from unstratified Kaplan-Meier estimates.
Time frame: From first dose of study medication to the occurrence of progression or death whichever came first, up to 44 months.
Area Under the Concentration-time Curve of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Area Under the Concentration-time Curve of Vinorelbine After Single and Multiple Intravenous Administrations of 25mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Maximum Measured Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Maximum Measured Concentration of Vinorelbine After Single and Multiple Intravenous Administrations of 25 mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Time From Dosing to the Maximum Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Time From Dosing to the Maximum Concentration of Vinorelbine After Single and Multiple Intravenous Administrations of 25mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Area Under the Concentration-time Curve of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 60mg/m^2 Per os Vinorelbine at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h,, 7h and 24h after dosing
Area Under the Concentration-time Curve of Vinorelbine After Multiple Administrations Per os of 60mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing
Maximum Measured Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 Per os Vinorelbine at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing
Maximum Measured Concentration of Vinorelbine After Multiple Administrations Per os of 60mg/m^2 in Presence and Absence of Afatinib at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing
Time From Dosing to the Maximum Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 60mg/m^2 Per os Vinorelbine at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing
Time From Dosing to the Maximum Concentration of Vinorelbine After Single and Multiple Administrations of 60mg/m^2 Vinorelbine Per os in Presence and Absence of Afatinib at Steady State
Time frame: 0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing