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CompletedNCT00906698Updated Jun 9, 2014Results posted

Afatinib and Vinorelbine in Tumours Known to Overexpress EGFR and/or HER2

A Phase 1 interventional study of BIBW 2992 low (20mg) dosage and BIBW 2992 medium (40mg) dosage in Neoplasms, sponsored by Boehringer Ingelheim. Completed at 2 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-06-09.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
55
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

To determine the maximum tolerated dose, safety, pharmacokinetics and anti-tumour efficacy of oral BIBW 2992 in combination with intravenous or oral vinorelbine

02

Conditions studied

  • Neoplasms
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histologically or cytologically confirmed diagnosis of malignancy that is now advanced, non resectable and/or metastatic
  • Tumours historically known to overexpress EGFR and/or HER2

Exclusion criteria

Exclusion criteria:

  • Prior treatment with HER2 inhibiting drugs within the past 4 weeks before the start of therapy or concomitantly with this trial.
  • Prior treatment with EGFR inhibiting drugs within the past two weeks before the start of therapy or concomitantly with this trial.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
55 participants (actual)

Study arms

  • Experimental
    BIBW 2992 and vinorelbine i.v

    Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine i.v.

    Drug: BIBW 2992 low (20mg) dosage · Drug: BIBW 2992 medium (40mg) dosage · Drug: BIBW 2992 high (50mg) dosage · Drug: Vinorelbine i.v. 25 mg/m²

  • Experimental
    BIBW 2992 and vinorelbine per os

    Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine per os.

    Drug: BIBW 2992 low (20mg) dosage · Drug: BIBW 2992 medium (40mg) dosage · Drug: BIBW 2992 high (50mg) dosage · Drug: Vinorelbine per os 60 mg/m² · Drug: Vinorelbine per os 80 mg/m²

Interventions

  • DrugBIBW 2992 low (20mg) dosage

    Patients will receive 20mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.

  • DrugBIBW 2992 medium (40mg) dosage

    Patients will receive 40mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.

  • DrugBIBW 2992 high (50mg) dosage

    Patients will receive 50mg dosage of BIBW 2992 plus standard dosage of vinorelbine.

  • DrugVinorelbine per os 60 mg/m²

    Patients will receive 60 mg/m² Vinorelbine per os at J1 J8 and J15

  • DrugVinorelbine per os 80 mg/m²

    Patients will receive 80 mg/m² Vinorelbine per os at J22

  • DrugVinorelbine i.v. 25 mg/m²

    Patients will receive 25 mg/m² of Vinorelbine i.v.

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

07

Results

Posted Apr 17, 2014

Participant flow

Participant flow — Overall Study
MilestoneAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Started31964185
Completed000000
Not completed31964185
Withdrew: Dose-limiting toxicity (dlt)060010
Withdrew: Adverse event002041
Withdrew: Disease progression31244124
Withdrew: Withdrawal by subject000010
Withdrew: Incl. non compliance, lost to follow-up010000

Outcome measures

PrimaryNumber 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
Reported as:
Number · participants
Number of Participants With Dose-limiting Toxicities (DLT)
participantsAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
First cycle (N=3;6;6;4;6;5)014013
Expansion cohort (N=0;13;0;0;12;0)NA7NANA2NA
SecondaryNumber 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.
Reported as:
Number · participants
Number of Patients With Best Overall Response
participantsAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Complete response000000
Partial response000030
Stable disease1105065
Progressive disease260470
Missing031020
SecondaryNumber 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.
Reported as:
Number · participants
Number of Patients With Objective Response (OR)
participantsAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Number of Patients With Objective Response (OR)000030
SecondaryNumber 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.
Reported as:
Number · participants
Number of Patients With Disease Control (DC)
participantsAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Number of Patients With Disease Control (DC)1105095
SecondaryTime 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.
Reported as:
Median · days
Time to Objective Response
daysAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Time to Objective Response————55 (55 to 343)—
SecondaryDuration 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.
Reported as:
Median · days
Duration of Objective Response
daysAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Duration of Objective Response————114 (113 to 151)—
SecondaryDuration 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.
Reported as:
Median · days
Duration of Disease Control
daysAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Duration of Disease Control110 (110 to 110)167 (94 to 351)168 (81 to 202)—162 (50 to 493)120 (54 to 230)
SecondaryBest 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.
Reported as:
Mean · percentage change in tumour size
Best Percentage Change in Tumour Size
percentage change in tumour sizeAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
Best Percentage Change in Tumour Size-5.65 ± 10.91-7.51 ± 4.22-24.10 ± 9.5725.89 ± 4.55-1.36 ± 9.62-10.76 ± 3.47
SecondaryProgression-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.
Reported as:
Median · weeks
Progression-free Survival (PFS)
weeksAfatinib 40mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine Per os
Progression-free Survival (PFS)14.6 (7.1 to 31.9)15.9 (7.4 to 23.7)
SecondaryArea 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
Reported as:
Geometric mean · ng*h/mL
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
ng*h/mLin Presence of Vinorelbine i.v.in Absence of Vinorelbine i.v.
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 State892 ± 87.3683 ± 375.0
Statistical analysis
  • in Presence of Vinorelbine i.v. vs in Absence of Vinorelbine i.v. · ANOVA · Ratio of adjusted gmean: 126.20 · 90% CI 69.549 to 229.012
SecondaryArea 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
Reported as:
Geometric mean · ng*h/mL
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
ng*h/mLin Presence of Afatinibin Absence of Afatinib
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 State512 ± 41.4655 ± 26.0
Statistical analysis
  • in Presence of Afatinib vs in Absence of Afatinib · ANOVA · Ratio of adjusted gmean: 75.58 · 90% CI 65.037 to 87.837
SecondaryMaximum 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
Reported as:
Geometric mean · ng/mL
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
ng/mLin Presence of Vinorelbine i.v.in Absence of Vinorelbine i.v.
Maximum Measured Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State62.0 ± 97.942.7 ± 425
Statistical analysis
  • in Presence of Vinorelbine i.v. vs in Absence of Vinorelbine i.v. · ANOVA · Ratio of adjusted gmean: 132.80 · 90% CI 72.305 to 243.917
SecondaryMaximum 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
Reported as:
Geometric mean · ng/mL
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
ng/mLin Presence of Afatinibin Absence of Afatinib
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 State822 ± 56.2941 ± 55.1
Statistical analysis
  • in Presence of Afatinib vs in Absence of Afatinib · ANOVA · Ratio of adjusted gmean: 83.80 · 90% CI 61.156 to 114.823
SecondaryTime 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
Reported as:
Median · hours
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
hoursin Presence of Vinorelbine i.v.in Absence of Vinorelbine i.v.
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 State3.16 (2.00 to 6.00)2.00 (1.00 to 4.03)
SecondaryTime 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
Reported as:
Median · hours
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
hoursin Presence of Afatinibin Absence of Afatinib
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 State0.166 (0.150 to 0.167)0.167 (0.150 to 0.233)
SecondaryArea 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
Reported as:
Geometric mean · ng*h/mL
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
ng*h/mLin Presence of Vinorelbine Per osin Absence of Vinorelbine Per os
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 State872 ± 39.81070 ± 33.8
Statistical analysis
  • in Presence of Vinorelbine Per os vs in Absence of Vinorelbine Per os · ANOVA · Ratio of adjusted gmean: 90.21 · 90% CI 76.071 to 106.978
SecondaryArea 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
Reported as:
Geometric mean · ng*h/mL
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
ng*h/mLin Presence of Afatinibin Absence of Afatinib
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 State258 ± 79.8334 ± 70.9
Statistical analysis
  • in Presence of Afatinib vs in Absence of Afatinib · ANOVA · Ratio of adjusted gmean: 76.75 · 90% CI 56.710 to 103.871
SecondaryMaximum 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
Reported as:
Geometric mean · ng/mL
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
ng/mLin Presence of Vinorelbine Per osin Absence of Vinorelbine Per os
Maximum Measured Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 Per os Vinorelbine at Steady State55.1 ± 35.667.2 ± 29.4
Statistical analysis
  • in Presence of Vinorelbine Per os vs in Absence of Vinorelbine Per os · ANOVA · Ratio of adjusted gmean: 83.86 · 95% CI 66.369 to 105.966
SecondaryMaximum 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
Reported as:
Geometric mean · ng/mL
Maximum Measured Concentration of Vinorelbine After Multiple Administrations Per os of 60mg/m^2 in Presence and Absence of Afatinib at Steady State
ng/mLin Presence of Afatinibin Absence of Afatinib
Maximum Measured Concentration of Vinorelbine After Multiple Administrations Per os of 60mg/m^2 in Presence and Absence of Afatinib at Steady State52.8 ± 80.865.0 ± 63.9
Statistical analysis
  • in Presence of Afatinib vs in Absence of Afatinib · ANOVA · Ratio of adjusted gmean: 81.70 · 90% CI 60.470 to 110.369
SecondaryTime 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
Reported as:
Median · hours
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
hoursin Presence of Vinorelbine Per osin Absence of Vinorelbine Per os
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 State3.54 (2.00 to 5.03)3.00 (1.00 to 6.00)
SecondaryTime 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
Reported as:
Median · hours
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
hoursin Presence of Afatinibin Absence of Afatinib
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 State1.50 (1.00 to 6.00)1.50 (0.917 to 3.17)

Adverse events

Collected over First administration of trial medication until 28 days after last administration of trial medication.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Afatinib 20mg With Vinorelbine i.v.—1/3 (33.3%)3/3 (100%)
Afatinib 40mg With Vinorelbine i.v.—11/19 (57.9%)19/19 (100%)
Afatinib 50mg With Vinorelbine i.v.—4/6 (66.7%)6/6 (100%)
Afatinib 20mg With Vinorelbine Per os—2/4 (50%)4/4 (100%)
Afatinib 40mg With Vinorelbine Per os—13/18 (72.2%)18/18 (100%)
Afatinib 50mg With Vinorelbine Per os—1/5 (20%)5/5 (100%)
Most frequent serious events
Showing 10 of 43
Most frequent serious events
EventAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
General physical health deteriorationGeneral disorders1/30/190/60/42/180/5
Gastrointestinal haemorrhageGastrointestinal disorders0/30/190/61/40/180/5
Respiratory failureRespiratory, thoracic and mediastinal disorders0/30/190/61/40/180/5
Orthostatic hypotensionVascular disorders0/30/190/61/40/180/5
DiarrhoeaGastrointestinal disorders0/33/191/60/42/181/5
VomitingGastrointestinal disorders0/30/191/60/42/181/5
Chest painGeneral disorders0/31/190/60/40/181/5
Back painMusculoskeletal and connective tissue disorders0/30/190/60/41/181/5
Mobility decreasedMusculoskeletal and connective tissue disorders0/30/190/60/40/181/5
DepressionPsychiatric disorders0/30/190/60/40/181/5
Most frequent other events
Showing 10 of 252
Most frequent other events
EventAfatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per os
AnaemiaBlood and lymphatic system disorders1/39/193/62/48/185/5
DiarrhoeaGastrointestinal disorders3/319/196/62/417/185/5
AstheniaGeneral disorders2/319/196/64/414/185/5
NauseaGastrointestinal disorders0/312/195/63/411/184/5
ParaesthesiaNervous system disorders0/34/195/61/45/181/5
NeutropeniaBlood and lymphatic system disorders2/312/193/61/48/184/5
Decreased appetiteMetabolism and nutrition disorders1/313/194/63/410/182/5
VomitingGastrointestinal disorders0/38/194/61/413/183/5
DyspepsiaGastrointestinal disorders2/31/191/61/43/181/5
StomatitisGastrointestinal disorders2/37/192/60/47/182/5

Baseline characteristics

Age, Continuous
Age, Continuous(years)Afatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per osTotal
Mean59.7 ± 15.355.3 ± 8.061.7 ± 5.055.3 ± 6.250.9 ± 9.551.0 ± 8.354.4 ± 9.0
Sex: Female, Male
Sex: Female, Male(Participants)Afatinib 20mg With Vinorelbine i.v.Afatinib 40mg With Vinorelbine i.v.Afatinib 50mg With Vinorelbine i.v.Afatinib 20mg With Vinorelbine Per osAfatinib 40mg With Vinorelbine Per osAfatinib 50mg With Vinorelbine Per osTotal
Female1114011431
Male28247124
08

Study locations

2 sites
  • 1200.69.3301 Boehringer Ingelheim Investigational Site
    Toulouse Cedex, France
  • 1200.69.3302 Boehringer Ingelheim Investigational Site
    Villejuif Cedex, France
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 9, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00906698
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
May 21, 2009
Start date
Jun 2009
Primary completion
Jan 2013
Completion
Jan 2013
Results posted
Apr 17, 2014
Last update
Jun 9, 2014

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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