Clinical Trial Results:
An open label, phase II trial of Afatinib with or without Vinorelbine for the treatment of HER2-overexpressing inflammatory breast cancer.
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
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Summary
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EudraCT number |
2010-024454-10 |
Trial protocol |
GB |
Global end of trial date |
18 Nov 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Apr 2016
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First version publication date |
06 Apr 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1200.89
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01325428 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Boehringer Ingelheim
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Sponsor organisation address |
Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
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Public contact |
QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim Pharma GmbH & Co. KG, +1 +1 800 243 0127, clintriage.rdg@boehringer-ingelheim.com
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Scientific contact |
QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim Pharma GmbH & Co. KG, +1 +1 800 243 0127, clintriage.rdg@boehringer-ingelheim.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Nov 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The objectives were to investigate the efficacy and safety of Afatinib alone and Afatinib in combination with weekly Vinorelbine upon progression on Afatinib monotherapy in patients with HER2-overexpressing inflammatory breast cancer (IBC).
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. If a subject continued to take trial medication, close monitoring was adhered to and all adverse events recorded. Rules were implemented whereby doses would be reduced if required. 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. Thereafter, if further events were reported which required dose reductions, the subject would be withdrawn from the trial. Symptomatic treatment of tumour associated symptoms were allowed throughout.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Dec 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Thailand: 12
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Country: Number of subjects enrolled |
Tunisia: 2
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Country: Number of subjects enrolled |
United Kingdom: 5
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Country: Number of subjects enrolled |
United States: 2
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Country: Number of subjects enrolled |
Australia: 2
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Country: Number of subjects enrolled |
Hong Kong: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 5
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Worldwide total number of subjects |
29
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
27
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
This was an open-label single arm 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). Patients continued from Part A to Part B upon progression of disease in Part A. | ||||||||||||||||||
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Pre-assignment
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Screening details |
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subjects) met all strictly implemented inclusion/exclusion criteria. Subjects were not allocated to trial treatment if any one of the specific entry criteria were violated. | ||||||||||||||||||
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Period 1
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Period 1 title |
Part A: Treatment Period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Part A: Afatinib Once Daily (OD). | ||||||||||||||||||
Arm 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. Patients were treated until PD in Part A, then they could continue with Afatinib and Vinorelbine in Part B. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Afatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD).
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline characteristics are based on patients who were randomised after successfully completing the screening period and received at least one of the trial medication. |
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Period 2
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Period 2 title |
Part B: Treatment Period
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Part B: Afatinib+V (Vinorelbine). | ||||||||||||||||||
Arm 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 at the previously applied dose in Part A 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. A patient was deemed to have completed the trial once they showed progressive disease according to RECIST (1.1) in Part B. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Vinorelbine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Vinorelbine was administered as 25 mg/m2 per week via intravenous (i.v) infusion.
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Investigational medicinal product name |
Afatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received Afatinib tablets, 40 mg taken orally Once Daily (OD).
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Baseline characteristics reporting groups
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Reporting group title |
Part A: Treatment Period
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Reporting 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. | ||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Afatinib Once Daily (OD). Afatinib+V (Vinorelbine).
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set 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.
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End points reporting groups
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Reporting group title |
Part A: Afatinib Once Daily (OD).
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Reporting 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. Patients were treated until PD in Part A, then they could continue with Afatinib and Vinorelbine in Part B. | ||
Reporting group title |
Part B: Afatinib+V (Vinorelbine).
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Reporting 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 at the previously applied dose in Part A 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. A patient was deemed to have completed the trial once they showed progressive disease according to RECIST (1.1) in Part B. | ||
Subject analysis set title |
Afatinib Once Daily (OD). Afatinib+V (Vinorelbine).
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Subject analysis set type |
Safety analysis | ||
Subject analysis set 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.
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End point 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). [1] | ||||||||
End point description |
Tumour response was assessed separately for Part A and Part B according to the Response Evaluation Criteria in SolidTumors (RECIST) version 1.1. The primary endpoint of this study was confirmed clinical benefit, as assessed by stable disease 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). The Confidence Interval (CI) is Exact CI.
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End point type |
Primary
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End point timeframe |
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.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis was tested. |
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| Notes [2] - Part A: TS |
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| No statistical analyses for this end point | |||||||||
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End point 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). [3] | ||||||||
End point 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 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). The Confidence Interval (CI) is Exact CI.
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End point type |
Primary
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End point timeframe |
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.
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis was tested. |
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| Notes [4] - Part B: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Confirmed Objective Response (OR) Assessed by RECIST 1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1). | ||||||||
End point description |
Objective response was defined on a patient level as a best response of CR or PR. The Confidence Interval (CI) is Exact CI.
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End point type |
Secondary
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End point timeframe |
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.
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| Notes [5] - Part A: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Confirmed Objective Response (OR) Assessed by RECIST 1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1). | ||||||||
End point description |
Objective response was defined on a patient level as a best response of CR or PR. The Confidence Interval (CI) is Exact CI.
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End point type |
Secondary
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End point timeframe |
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.
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| Notes [6] - Part B: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Unconfirmed Objective Response (OR) Assessed by RECIST 1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1). | ||||||||
End point description |
Objective response was defined on a patient level as a best response of CR or PR. The Confidence Interval (CI) is Exact CI.
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End point type |
Secondary
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End point timeframe |
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.
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| Notes [7] - Part A: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Unconfirmed Objective Response (OR) Assessed by RECIST 1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1). | ||||||||
End point description |
Objective response was defined on a patient level as a best response of CR or PR. The Confidence Interval (CI) is Exact CI.
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End point type |
Secondary
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End point timeframe |
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.
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| Notes [8] - Part B: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Duration of Unconfirmed Objective Response. | ||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
From first drug administration until end of Part B, up to 929 days.
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| Notes [9] - Part B: TS. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Duration of Unconfirmed Objective Response. | ||||||||
End point description |
Objective response was defined on a patient level as a best response of CR (Complete Response) or PR (Partial Response). 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-Progression Free Survival). 99999: Median is not calculable as the KM probability never falls to 0.5 therefore it can't be estimated.
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End point type |
Secondary
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End point timeframe |
From first drug administration until end of Part A, up to 929 days.
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| Notes [10] - Part A: TS. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Progression Free Survival. | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
From first drug administration until end of Part A, up to 713 days.
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| Notes [11] - Part A: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Progression Free Survival. | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
From first drug administration until end of Part B, up to 230 days.
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| Notes [12] - Part B: TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival Over the Whole Sudy. | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
From first drug administration until end of study, up to 700 days.
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| Notes [13] - TS |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
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).
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Adverse event reporting additional 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.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Part A: Afatinib Once Daily (OD).
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B: Afatinib+V (Vinorelbine).
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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18 Oct 2012 |
This amendment introduced a number of minor clarifications or updates of study procedures, administrative changes (such as updating the address of the coordinating investigator and including a citation for recently published data in place of previously unpublished data), and corrections to ensure consistency between the synopsis and the main text of the protocol and between different sections of the protocol. Changes to study procedures included the following: 1. A fresh tissue biopsy could be taken up to 2 days before C1V1. 2. No ECG was required at Day 15 of Course 1 in Part B. 3. Dispensing of trial medication was not required at the EOT visit in Part B. 4. It was clarified that patients having a short course palliative radiotherapy had to have a tumour assessment within 14 days of the first dose of Vinorelbine. 5. A statement on risk of keratitis and ulcerative keratitis was added since the European Medicines Agency (EMA) has requested a class labelling following treatment with currently approved EGFR inhibitors for cancer. 6. Exclusion criterion no. 7 was clarified: bilateral primary breast cancer, metastases to the contralateral breast. 7. Exclusion criterion no. 14 and the text of the CTP regarding dose adjustments with Vinorelbine was updated to be consistent with a newly released SmPC for Vinorelbine. 8. Exclusion criterion no. 17 was amended to allow higher values of ALT/AST (changed from 2.5 to 3 x ULN). 9. Exclusion criterion no. 26 was clarified to indicate that Trastuzumab failure patients had to have received Trastuzumab. 10. The time between first and second dose of afatinib could be less than 24 h. 11. The type of MRI to be used to assess brain lesions was updated. 12. The reporting of the worsening of underlying disease or other pre-existing conditions, and the change in vital signs, ECG, physical examination and laboratory tests results was amended as requested by regulatory authorities. |
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01 Jul 2013 |
This amendment introduced major changes to the study design. The reasons for the changes were slow recruitment of Trastuzumab-failure patients into Part A of the study (7 in total at 17 Jun 2013) plus a change in the benefit/risk of the combination of Afatinib and Vinorelbine (experimental arm). For BI trial 1200.75, an independent DMC conducted a benefit risk analysis when over half of the planned number of patients had been enrolled. The PFS analysis showed a low likelihood of the 1200.75 study meeting the pre-defined criteria for increased efficacy combined with an increased rate of treatment discontinuation and dose reduction and a higher rate of SAEs and deaths in the Afatinib and Vinorelbine arm of the study. The DMC recommended discontinuing recruitment into the 1200.75 trial. Boehringer Ingelheim decided to stop further randomisation into trial 1200.75 and to discontinue further treatment with the combination of Afatinib and Vinorelbine as of 26 Apr 2013. Boehringer Ingelheim decided as a precautionary measure, to stop the inclusion of new patients into Part B of the present study on 03 May 2013. Also, any patients in screening for Part B at that date were not permitted to start treatment. Due to the slow recruitment, it was also decided to stop further inclusion of patients into Part A. In addition, it was clarified that tumour assessments were to be performed in Part B every 8 weeks from the first dose of Vinorelbine. Also, precautionary information added regarding ILD (in line with the standard wording in other Afatinib trials) and keratitis (at the request of the French Health Authority for all Afatinib trials). |
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10 Apr 2014 |
After the introduction of protocol amendment 2 recruitment for trial 1200.89 was ceased before it was fully completed. Therefore when protocol amendment 3 was implemented, there were only a few patients still receiving trial medication. Rather than perform the primary analysis and update it shortly thereafter, it was considered better to wait until most or all patients had progressed or started further treatment. No changes were made to the analysis only to the timing. To allow flexibility as to when the primary analysis was to be performed, the sentence regarding timing was updated. Additionally, collection of Observation Period data was no longer considered necessary. Patients still benefiting from treatment were to continue to receive trial medication. However, once they ceased trial medication they were to complete their study participation at the time of their last follow-up visit and did not enter the observation period. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| 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. | |||||||
