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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01325428
First received: March 28, 2011
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
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 Intervention Phase
Breast Neoplasms
Drug: Afatinib once daily (OD)
Drug: Vinorelbine Weekly
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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).

  • 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. ] [ Designated as safety issue: No ]
    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:
  • 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. ] [ Designated as safety issue: No ]
    Objective response was defined on a patient level as a best response of CR or PR.

  • 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. ] [ Designated as safety issue: No ]
    Objective response was defined on a patient level as a best response of CR or PR.

  • 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. ] [ Designated as safety issue: No ]
    Objective response was defined on a patient level as a best response of CR or PR.

  • 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. ] [ Designated as safety issue: No ]
    Objective response was defined on a patient level as a best response of CR or PR.

  • Part A: Duration of Unconfirmed Objective Response. [ Time Frame: From first drug administration until end of Part A, up to 929 days. ] [ Designated as safety issue: No ]
    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)).

  • Part B: Duration of Unconfirmed Objective Response. [ Time Frame: From first drug administration until end of Part B, up to 929 days. ] [ Designated as safety issue: No ]
    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).

  • Part A: Progression Free Survival. [ Time Frame: From first drug administration until end of Part A, up to 713 days. ] [ Designated as safety issue: No ]
    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.

  • Part B: Progression Free Survival. [ Time Frame: From first drug administration until end of Part B, up to 230 days. ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival Over the Whole Sudy. [ Time Frame: From first drug administration until end of study, up to 700 days. ] [ Designated as safety issue: No ]
    PD was evaluated according to the RECIST version 1.1. Number of days from the start of monotherapy to the date of second PD.


Enrollment: 26
Study Start Date: August 2011
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01325428

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

Additional Information:
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01325428     History of Changes
Other Study ID Numbers: 1200.89  2010-024454-10 
Study First Received: March 28, 2011
Results First Received: November 17, 2015
Last Updated: June 17, 2016
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Hong Kong: Department of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Thailand: Food and Drug Administration
Tunisia: Ministry of Public Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 23, 2016