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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00906698
First received: May 14, 2009
Last updated: March 21, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Neoplasms
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
Drug: Vinorelbine i.v. 25 mg/m²
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Open Label Trial to Assess Safety of BIBW 2992 With Vinorelbine in Solid Tumors Known to Overexpress HER2 and/or EGFR

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Participants With Dose-limiting Toxicities (DLT) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Patients With Best Overall Response [ 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. ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Objective Response (OR) [ 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. ] [ Designated as safety issue: No ]
    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).

  • Number of Patients With Disease Control (DC) [ 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. ] [ Designated as safety issue: No ]
    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 to Objective Response [ 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. ] [ Designated as safety issue: No ]
    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.

  • Duration of Objective Response [ 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. ] [ Designated as safety issue: No ]
    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.

  • Duration of Disease Control [ 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. ] [ Designated as safety issue: No ]
    Duration of disease control was measured from the start of study treatment to the time of progression or death, whichever occured first.

  • Best Percentage Change in Tumour Size [ Time Frame: Screening and every 8 weeks after starting of treatment, up to 44 weeks. ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival (PFS) [ Time Frame: From first dose of study medication to the occurrence of progression or death whichever came first, up to 44 months. ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: June 2009
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Patients will receive 20mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.
Drug: BIBW 2992 medium (40mg) dosage
Patients will receive 40mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.
Drug: BIBW 2992 high (50mg) dosage
Patients will receive 50mg dosage of BIBW 2992 plus standard dosage of vinorelbine.
Drug: Vinorelbine i.v. 25 mg/m²
Patients will receive 25 mg/m² of Vinorelbine i.v.
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
Patients will receive 20mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.
Drug: BIBW 2992 medium (40mg) dosage
Patients will receive 40mg dosage per day of BIBW 2992 plus standard dosage of vinorelbine.
Drug: BIBW 2992 high (50mg) dosage
Patients will receive 50mg dosage of BIBW 2992 plus standard dosage of vinorelbine.
Drug: Vinorelbine per os 60 mg/m²
Patients will receive 60 mg/m² Vinorelbine per os at J1 J8 and J15
Drug: Vinorelbine per os 80 mg/m²
Patients will receive 80 mg/m² Vinorelbine per os at J22

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00906698

Locations
France
1200.69.3301 Boehringer Ingelheim Investigational Site
Toulouse Cedex, France
1200.69.3302 Boehringer Ingelheim Investigational Site
Villejuif Cedex, France
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00906698     History of Changes
Other Study ID Numbers: 1200.69, 2008-006290-32
Study First Received: May 14, 2009
Results First Received: January 10, 2014
Last Updated: March 21, 2014
Health Authority: France: AFFSAPS

Additional relevant MeSH terms:
Neoplasms
Vinorelbine
Vinblastine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014