Afatinib (BIBW2992) in HER2 (Human Epidermal Growth Factor Receptor 2)-Overexpressing Inflammatory Breast Cancer

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01325428
• Collaborator: (none)
• Enrollment: 26
• Locations: 16
• Arm: 1
• Duration (Months): 39
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The general aim of this study is to investigate the efficacy and safety of afatinib alone and in combination with weekly vinorelbine (in patients who progress on afatinib monotherapy within this trial) as treatment in patients with HER2-overexpressing, locally advanced or metastatic inflammatory breast cancer. The study will include patients who have and have not failed prior trastuzumab treatment.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Afatinib once daily (OD); Drug: Vinorelbine Weekly	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Phase II Trial of Afatinib With or Without Vinorelbine for the Treatment of HER2-overexpressing Inflammatory Breast Cancer
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afatinib once daily (OD) Patients receive afatinib monotherapy once daily until progression of their disease	Drug: Afatinib once daily (OD); Patient to receive afatinib monotherapy until progression of their disease; Drug: Vinorelbine Weekly; Patients additionally receive vinorelbine weekly on disease progression on afatinib monotherapy

Outcome Measures

Primary Outcome Measures

1. Part A: Clinical Benefit (CB) Assessed by Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at Least 6 Months Using the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). [This endpoint was assessed between the from first administration of trial medication in Part A and the earliest of PD, death or start of next treatment (either Part B combination therapy or new anti-cancer therapy) up to 929 days.]

   Tumour response was assessed separately for Part A and Part B according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoint of this study was confirmed clinical benefit, as assessed by Stable Disease (SD) for at least 6 months (defined as >182 days), Partial Response (PR), or Complete Response (CR) according to RECIST version 1.1 (only confirmed responses were considered).

2. Part B: Clinical Benefit (CB) Assessed by Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at Least 6 Months Using the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). [This endpoint was recorded from first administration of trial medication in Part B until the earliest of PD, death or start of new anti-cancer therapy up to 929 days.]

   Tumour response was assessed separately for Part B according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoint of this study was confirmed clinical benefit, as assessed by Stable Disease (SD) for at least 6 months (defined as >182 days), Partial Response (PR), or Complete Response (CR) according to RECIST version 1.1 (only confirmed responses were considered).

Secondary Outcome Measures

1. Part A: Confirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1). [This endpoint was recorded from first administration of trial medication until the earliest of disease progression, death or start of next treatment (either Part B combination therapy or new anti-cancer therapy) up to 929 days.]

   Objective response was defined on a patient level as a best response of CR or PR.

2. Part B: Confirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1). [This endpoint was recorded from first administration of trial medication in Part B and until the earliest of disease progression, death or start of new anti-cancer therapy up to 929 days.]

   Objective response was defined on a patient level as a best response of CR or PR.

3. Part A: Unconfirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1). [This endpoint was recorded from first administration of trial medication until the earliest of PD, death or start of next treatment (either Part B combination therapy or new anti-cancer therapy) up to 929 days.]

   Objective response was defined on a patient level as a best response of CR or PR.

4. Part B: Unconfirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1 ). [This endpoint was recorded from first administration of trial medication in Part B and until the earliest of PD, death or start of new anti-cancer therapy up to 929 days.]

   Objective response was defined on a patient level as a best response of CR or PR.

5. Part A: Duration of Unconfirmed Objective Response. [From first drug administration until end of Part A, up to 929 days.]

   Objective Response (OR) was defined on a patient level as a best response of Complete Response (CR) or Partial Response (PR). Duration of objective response was measured from the time of first unconfirmed objective response to the time of progression or death (or date of censoring for Progression Free Survival (PFS)).

6. Part B: Duration of Unconfirmed Objective Response. [From first drug administration until end of Part B, up to 929 days.]

   Objective response was defined on a patient level as a best response of CR or PR. Duration of objective response was measured from the time of first unconfirmed objective response to the time of progression or death (or date of censoring for PFS).

7. Part A: Progression Free Survival. [From first drug administration until end of Part A, up to 713 days.]

   PD was evaluated according to the RECIST version 1.1. For patients with a known date of progression (or death), PFS was the earlier of date of progression or death - date of first administration + 1. The date of progression and date of first administration referred to the respective part of the study A.

8. Part B: Progression Free Survival. [From first drug administration until end of Part B, up to 230 days.]

   PD was evaluated according to the RECIST version 1.1. For patients with a known date of progression (or death), PFS was the earlier of date of progression or death - date of first administration + 1. The date of progression and date of first administration referred to the respective part of the study B.

9. Progression Free Survival Over the Whole Sudy. [From first drug administration until end of study, up to 700 days.]

   PD was evaluated according to the RECIST version 1.1. Number of days from the start of monotherapy to the date of second PD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Female patients >=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer

2. Locally advanced or metastatic disease

3. Must have disease that can be evaluated according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1)

4. For trastuzumab pre-treated patients, must have failed prior trastuzumab treatment

5. Investigator-confirmed diagnosis of Inflammatory Breast Cancer

6. Must have biopsiable disease

Exclusion criteria:

1. Prior treatment with HER2-targeted small molecules or antibodies other than trastuzumab (which must have been given in the trastuzumab-failure study population)

2. Must not have received prior vinorelbine treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1200.89.10001 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
2	1200.89.10005 Boehringer Ingelheim Investigational Site	Durham	North Carolina	United States
3	1200.89.61002 Boehringer Ingelheim Investigational Site	East Bentleigh	Victoria	Australia
4	1200.89.61003 Boehringer Ingelheim Investigational Site	Perth	Western Australia	Australia
5	1200.89.85201 Boehringer Ingelheim Investigational Site	Hong Kong		Hong Kong
6	1200.89.82001 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
7	1200.89.82002 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
8	1200.89.66002 Boehringer Ingelheim Investigational Site	Bangkok		Thailand
9	1200.89.66004 Boehringer Ingelheim Investigational Site	Bangkok		Thailand
10	1200.89.66003 Boehringer Ingelheim Investigational Site	Chiangmai		Thailand
11	1200.89.66001 Boehringer Ingelheim Investigational Site	Hat-Yai, Songkhla		Thailand
12	1200.89.21601 Boehringer Ingelheim Investigational Site	Ariana		Tunisia
13	1200.89.21602 Boehringer Ingelheim Investigational Site	Sousse		Tunisia
14	1200.89.44002 Boehringer Ingelheim Investigational Site	Bournemouth		United Kingdom
15	1200.89.44001 Boehringer Ingelheim Investigational Site	London		United Kingdom
16	1200.89.44003 Boehringer Ingelheim Investigational Site	London		United Kingdom

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01325428
• Other Study ID Numbers: 1200.89; 2010-024454-10
• First Posted: Mar 29, 2011
• Last Update Posted: Jul 19, 2016
• Last Verified: Jun 1, 2016

• Additional relevant MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms; Vinorelbine; Afatinib

Study Results

Participant Flow

Recruitment Details	This was an open-label study conducted in two sequential parts (Part A in which patients were treated with Afatinib (BIBW 2992) as monotherapy; Part B in which patients were treated with Afatinib plus Vinorelbine as combination therapy after progression on Afatinib monotherapy).
Pre-assignment Detail	Part A: Patients were treated with Afatinib and could continue on treatment until first Progression of Disease (PD), intolerable side effects, or withdrawal of consent. Upon first PD, patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with weekly Vinorelbine.

Arm/Group Title	Afatinib (Part A). Afatinib+V (Vinorelbine) (Part B).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until Progression of their Disease (PD). In case of treatment-related adverse events (AEs), the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily. Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent.
Period Title: Part A
STARTED	26
COMPLETED	10
NOT COMPLETED	16
Period Title: Part A
STARTED	10
COMPLETED	7
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Part A: Afatinib Once Daily. Part B: Afatinib+V (Vinorelbine).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until Progression of their Disease (PD). In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily. Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent.
Overall Participants	26
Age, Customized (Years) [Mean (Standard Deviation) ]
Part A	51.5 (8.8)
Part B	51.5 (12.5)
Sex/Gender, Customized (Number) [Number]
Female (Part A)	26 100%
Female (Part B)	10 38.5%
Male (Part A)	0 0%
Male (Part B)	0 0%

Outcome Measures

1. Primary Outcome

Title	Part A: Clinical Benefit (CB) Assessed by Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at Least 6 Months Using the Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
Description	Tumour response was assessed separately for Part A and Part B according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoint of this study was confirmed clinical benefit, as assessed by Stable Disease (SD) for at least 6 months (defined as >182 days), Partial Response (PR), or Complete Response (CR) according to RECIST version 1.1 (only confirmed responses were considered).
Time Frame	This endpoint was assessed between the from first administration of trial medication in Part A and the earliest of PD, death or start of next treatment (either Part B combination therapy or new anti-cancer therapy) up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.

Arm/Group Title	Part A: Afatinib Once Daily (OD).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until PD. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	26
Number (95% Confidence Interval) [Percentage of participants]	35 134.6%

2. Primary Outcome

Title	Part B: Clinical Benefit (CB) Assessed by Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at Least 6 Months Using the Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
Description	Tumour response was assessed separately for Part B according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoint of this study was confirmed clinical benefit, as assessed by Stable Disease (SD) for at least 6 months (defined as >182 days), Partial Response (PR), or Complete Response (CR) according to RECIST version 1.1 (only confirmed responses were considered).
Time Frame	This endpoint was recorded from first administration of trial medication in Part B until the earliest of PD, death or start of new anti-cancer therapy up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.

Arm/Group Title	Part B: Afatinib Once Daily (OD)+V (Vinorelbine).
Arm/Group Description	Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	10
Number (95% Confidence Interval) [Percentage of participants]	20 76.9%

3. Secondary Outcome

Title	Part A: Confirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1).
Description	Objective response was defined on a patient level as a best response of CR or PR.
Time Frame	This endpoint was recorded from first administration of trial medication until the earliest of disease progression, death or start of next treatment (either Part B combination therapy or new anti-cancer therapy) up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.

Arm/Group Title	Part A: Afatinib Once Daily (OD).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until progression of their disease. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	26
Number (95% Confidence Interval) [Percentage of participants]	31 119.2%

4. Secondary Outcome

Title	Part B: Confirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1).
Description	Objective response was defined on a patient level as a best response of CR or PR.
Time Frame	This endpoint was recorded from first administration of trial medication in Part B and until the earliest of disease progression, death or start of new anti-cancer therapy up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.

Arm/Group Title	Part B: Afatinib Once Daily (OD)+V (Vinorelbine).
Arm/Group Description	Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	10
Number (95% Confidence Interval) [Percentage of participants]	10 38.5%

5. Secondary Outcome

Title	Part A: Unconfirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1).
Description	Objective response was defined on a patient level as a best response of CR or PR.
Time Frame	This endpoint was recorded from first administration of trial medication until the earliest of PD, death or start of next treatment (either Part B combination therapy or new anti-cancer therapy) up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.

Arm/Group Title	Part A: Afatinib Once Daily (OD).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until progression of their disease. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	26
Number (95% Confidence Interval) [Percentage of participants]	42 161.5%

6. Secondary Outcome

Title	Part B: Unconfirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1 ).
Description	Objective response was defined on a patient level as a best response of CR or PR.
Time Frame	This endpoint was recorded from first administration of trial medication in Part B and until the earliest of PD, death or start of new anti-cancer therapy up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.

Arm/Group Title	Part B: Afatinib Once Daily (OD)+V (Vinorelbine).
Arm/Group Description	Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	10
Number (95% Confidence Interval) [Percentage of participants]	30 115.4%

7. Secondary Outcome

Title	Part A: Duration of Unconfirmed Objective Response.
Description	Objective Response (OR) was defined on a patient level as a best response of Complete Response (CR) or Partial Response (PR). Duration of objective response was measured from the time of first unconfirmed objective response to the time of progression or death (or date of censoring for Progression Free Survival (PFS)).
Time Frame	From first drug administration until end of Part A, up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.

Arm/Group Title	Part A: Afatinib Once Daily (OD).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until progression of their disease. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily.
Measure Participants	11
Median (95% Confidence Interval) [Days]	NA

8. Secondary Outcome

Title	Part B: Duration of Unconfirmed Objective Response.
Description	Objective response was defined on a patient level as a best response of CR or PR. Duration of objective response was measured from the time of first unconfirmed objective response to the time of progression or death (or date of censoring for PFS).
Time Frame	From first drug administration until end of Part B, up to 929 days.

Outcome Measure Data

Analysis Population Description

TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.

Arm/Group Title	Part B: Afatinib Once Daily (OD)+V (Vinorelbine).
Arm/Group Description	Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	3
Median (95% Confidence Interval) [Days]	57

9. Secondary Outcome

Title	Part A: Progression Free Survival.
Description	PD was evaluated according to the RECIST version 1.1. For patients with a known date of progression (or death), PFS was the earlier of date of progression or death - date of first administration + 1. The date of progression and date of first administration referred to the respective part of the study A.
Time Frame	From first drug administration until end of Part A, up to 713 days.

Outcome Measure Data

Analysis Population Description

TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.

Arm/Group Title	Part A: Afatinib Once Daily (OD).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until progression of their disease. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily.
Measure Participants	26
Median (95% Confidence Interval) [Days]	110.5

10. Secondary Outcome

Title	Part B: Progression Free Survival.
Description	PD was evaluated according to the RECIST version 1.1. For patients with a known date of progression (or death), PFS was the earlier of date of progression or death - date of first administration + 1. The date of progression and date of first administration referred to the respective part of the study B.
Time Frame	From first drug administration until end of Part B, up to 230 days.

Outcome Measure Data

Analysis Population Description

TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.

Arm/Group Title	Part B: Afatinib Once Daily (OD)+V (Vinorelbine).
Arm/Group Description	Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	10
Median (95% Confidence Interval) [Days]	106.0

11. Secondary Outcome

Title	Progression Free Survival Over the Whole Sudy.
Description	PD was evaluated according to the RECIST version 1.1. Number of days from the start of monotherapy to the date of second PD.
Time Frame	From first drug administration until end of study, up to 700 days.

Outcome Measure Data

Analysis Population Description

TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A. TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.

Arm/Group Title	Afatinib Once Daily (OD). Afatinib+V (Vinorelbine).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until PD. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily. Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent. The 95% Confidence Interval is Exact Confidence Interval.
Measure Participants	26
Median (95% Confidence Interval) [Days]	253.0

Adverse Events

Time Frame	Part A: From first study drug administration in Part A to last study drug administration in Part A + up to 28 days (max. 728). Part B: From first study drug administration in Part B to last study drug administration in Part B + up to 28 days (max. 265).
Adverse Event Reporting Description	The additional 28 days is the residual effect period which was added to the last study drug administration in each part. This may have been truncated in Part A where patients started Vinorelbine prior to the 28 days elapsing.
Arm/Group Title	Part A: Afatinib Once Daily (OD).		Part B: Afatinib+V (Vinorelbine).
Arm/Group Description	Part A: Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD) until progression of their disease. In case of treatment-related AEs, the 40 mg dose could be reduced by increments of 10 mg to 30 mg once daily or 20 mg once daily.		Part B: Upon first Progression of Disease (PD), patients could enter Part B of the study, during which they continued to be treated with Afatinib and additionally were treated with Vinorelbine 25 mg/m2 per week via intravenous (i.v) infusion. Patients treated with Afatinib and Vinorelbine combination therapy could continue to receive treatment until second progression of disease, intolerable side effects, or withdrawal of consent.
All Cause Mortality
	Part A: Afatinib Once Daily (OD).		Part B: Afatinib+V (Vinorelbine).
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Afatinib Once Daily (OD).		Part B: Afatinib+V (Vinorelbine).
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/26 (46.2%)		4/10 (40%)
Gastrointestinal disorders
Abdominal pain	0/26 (0%)		1/10 (10%)
Diarrhoea	3/26 (11.5%)		1/10 (10%)
Nausea	0/26 (0%)		1/10 (10%)
Vomiting	3/26 (11.5%)		1/10 (10%)
General disorders
Asthenia	0/26 (0%)		1/10 (10%)
Fatigue	1/26 (3.8%)		0/10 (0%)
Pain	1/26 (3.8%)		0/10 (0%)
Hepatobiliary disorders
Hepatic lesion	1/26 (3.8%)		0/10 (0%)
Infections and infestations
Abscess limb	1/26 (3.8%)		0/10 (0%)
Cellulitis	1/26 (3.8%)		0/10 (0%)
Lower respiratory tract infection	1/26 (3.8%)		0/10 (0%)
Sepsis	1/26 (3.8%)		0/10 (0%)
Urinary tract infection	1/26 (3.8%)		0/10 (0%)
Injury, poisoning and procedural complications
Hepatic haematoma	0/26 (0%)		1/10 (10%)
Wound complication	1/26 (3.8%)		0/10 (0%)
Metabolism and nutrition disorders
Hyperphosphataemia	1/26 (3.8%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/26 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/26 (3.8%)		0/10 (0%)
Metastases to central nervous system	1/26 (3.8%)		0/10 (0%)
Metastases to liver	1/26 (3.8%)		0/10 (0%)
Tumour haemorrhage	1/26 (3.8%)		0/10 (0%)
Nervous system disorders
Headache	0/26 (0%)		1/10 (10%)
Renal and urinary disorders
Renal failure	1/26 (3.8%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/26 (3.8%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Afatinib Once Daily (OD).		Part B: Afatinib+V (Vinorelbine).
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	4/26 (15.4%)		5/10 (50%)
Neutropenia	1/26 (3.8%)		8/10 (80%)
Cardiac disorders
Atrial flutter	0/26 (0%)		1/10 (10%)
Eye disorders
Dry eye	3/26 (11.5%)		0/10 (0%)
Panophthalmitis	0/26 (0%)		1/10 (10%)
Gastrointestinal disorders
Abdominal pain	0/26 (0%)		2/10 (20%)
Abdominal pain upper	2/26 (7.7%)		1/10 (10%)
Diarrhoea	23/26 (88.5%)		6/10 (60%)
Dry mouth	2/26 (7.7%)		0/10 (0%)
Nausea	7/26 (26.9%)		5/10 (50%)
Stomatitis	3/26 (11.5%)		1/10 (10%)
Vomiting	7/26 (26.9%)		1/10 (10%)
General disorders
Catheter site erythema	0/26 (0%)		1/10 (10%)
Fatigue	4/26 (15.4%)		5/10 (50%)
Mucosal inflammation	10/26 (38.5%)		3/10 (30%)
Pyrexia	1/26 (3.8%)		2/10 (20%)
Infections and infestations
Abscess limb	0/26 (0%)		1/10 (10%)
Cellulitis	0/26 (0%)		1/10 (10%)
Cystitis	1/26 (3.8%)		1/10 (10%)
Eye infection	0/26 (0%)		1/10 (10%)
Paronychia	9/26 (34.6%)		0/10 (0%)
Rhinitis	0/26 (0%)		1/10 (10%)
Upper respiratory tract infection	2/26 (7.7%)		2/10 (20%)
Injury, poisoning and procedural complications
Allergic transfusion reaction	0/26 (0%)		1/10 (10%)
Contusion	0/26 (0%)		1/10 (10%)
Fall	0/26 (0%)		1/10 (10%)
Procedural haemorrhage	0/26 (0%)		1/10 (10%)
Investigations
Alanine aminotransferase increased	4/26 (15.4%)		0/10 (0%)
Aspartate aminotransferase increased	4/26 (15.4%)		0/10 (0%)
Blood alkaline phosphatase increased	2/26 (7.7%)		0/10 (0%)
Blood creatine phosphokinase increased	0/26 (0%)		1/10 (10%)
Neutrophil count decreased	0/26 (0%)		1/10 (10%)
Weight decreased	7/26 (26.9%)		4/10 (40%)
White blood cell count decreased	0/26 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	10/26 (38.5%)		2/10 (20%)
Hypokalaemia	5/26 (19.2%)		1/10 (10%)
Hypomagnesaemia	2/26 (7.7%)		0/10 (0%)
Hyponatraemia	0/26 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/26 (0%)		1/10 (10%)
Muscle spasms	1/26 (3.8%)		1/10 (10%)
Myalgia	1/26 (3.8%)		2/10 (20%)
Pain in extremity	0/26 (0%)		1/10 (10%)
Nervous system disorders
Dizziness	2/26 (7.7%)		3/10 (30%)
Headache	3/26 (11.5%)		1/10 (10%)
Memory impairment	0/26 (0%)		1/10 (10%)
Migraine	0/26 (0%)		1/10 (10%)
Neuropathy peripheral	1/26 (3.8%)		1/10 (10%)
Reproductive system and breast disorders
Breast pain	2/26 (7.7%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	0/26 (0%)		1/10 (10%)
Dyspnoea	0/26 (0%)		2/10 (20%)
Epistaxis	4/26 (15.4%)		0/10 (0%)
Oropharyngeal pain	0/26 (0%)		1/10 (10%)
Pleural effusion	0/26 (0%)		1/10 (10%)
Rhinorrhoea	0/26 (0%)		1/10 (10%)
Skin and subcutaneous tissue disorders
Alopecia	0/26 (0%)		1/10 (10%)
Dermatitis	1/26 (3.8%)		1/10 (10%)
Dermatitis acneiform	5/26 (19.2%)		0/10 (0%)
Dry skin	2/26 (7.7%)		1/10 (10%)
Erythema	3/26 (11.5%)		1/10 (10%)
Fungating wound	0/26 (0%)		1/10 (10%)
Hand dermatitis	0/26 (0%)		1/10 (10%)
Palmar-plantar erythrodysaesthesia syndrome	3/26 (11.5%)		1/10 (10%)
Pruritus	2/26 (7.7%)		0/10 (0%)
Rash	17/26 (65.4%)		1/10 (10%)
Skin lesion	2/26 (7.7%)		0/10 (0%)
Vascular disorders
Lymphoedema	1/26 (3.8%)		1/10 (10%)

Limitations/Caveats

Boehringer Ingelheim (BI) decided to stop further inclusion of patients and stop further treatment with the combination of Afatinib and Vinorelbine as of 03-May-2013. Recruitment into the trial was stopped by amendment in Jul 2013.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.