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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	26 participants
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 :	August 2011
Actual Primary Completion Date :	November 2014
Actual Study Completion Date :	November 2014

Arms and Interventions

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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

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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). [ 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. ]
   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). [ 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. ]
   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). [ 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. ]
   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). [ 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. ]
   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). [ 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. ]
   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 ). [ 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. ]
   Objective response was defined on a patient level as a best response of CR or PR.
5. Part A: Duration of Unconfirmed Objective Response. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

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Locations

United States, California
1200.89.10001 Boehringer Ingelheim Investigational Site
Los Angeles, California, United States
United States, North Carolina
1200.89.10005 Boehringer Ingelheim Investigational Site
Durham, North Carolina, United States
Australia, Victoria
1200.89.61002 Boehringer Ingelheim Investigational Site
East Bentleigh, Victoria, Australia
Australia, Western Australia
1200.89.61003 Boehringer Ingelheim Investigational Site
Perth, Western Australia, Australia
Hong Kong
1200.89.85201 Boehringer Ingelheim Investigational Site
Hong Kong, Hong Kong
Korea, Republic of
1200.89.82001 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1200.89.82002 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
Thailand
1200.89.66002 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1200.89.66004 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1200.89.66003 Boehringer Ingelheim Investigational Site
Chiangmai, Thailand
1200.89.66001 Boehringer Ingelheim Investigational Site
Hat-Yai, Songkhla, Thailand
Tunisia
1200.89.21601 Boehringer Ingelheim Investigational Site
Ariana, Tunisia
1200.89.21602 Boehringer Ingelheim Investigational Site
Sousse, Tunisia
United Kingdom
1200.89.44002 Boehringer Ingelheim Investigational Site
Bournemouth, United Kingdom
1200.89.44001 Boehringer Ingelheim Investigational Site
London, United Kingdom
1200.89.44003 Boehringer Ingelheim Investigational Site
London, United Kingdom

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair:	Boehringer Ingelheim	Boehringer Ingelheim

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goh G, Schmid R, Guiver K, Arpornwirat W, Chitapanarux I, Ganju V, Im SA, Kim SB, Dechaphunkul A, Maneechavakajorn J, Spector N, Yau T, Afrit M, Ahmed SB, Johnston SR, Gibson N, Uttenreuther-Fischer M, Herrero J, Swanton C. Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine. PLoS Med. 2016 Dec 6;13(12):e1002136. doi: 10.1371/journal.pmed.1002136. eCollection 2016 Dec.

Responsible Party:	Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT01325428 History of Changes
Other Study ID Numbers:	1200.89; 2010-024454-10 ( EudraCT Number: EudraCT )
First Posted:	March 29, 2011
Results First Posted:	February 11, 2016
Last Update Posted:	July 19, 2016
Last Verified:	June 2016

Additional relevant MeSH terms:

Breast Neoplasms; Inflammatory Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Vinorelbine	Vinblastine; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action