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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Afatinib once daily (OD)

Vinorelbine Weekly

About this trial

This is an interventional treatment trial for Breast Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria:

Female patients >=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer
Locally advanced or metastatic disease
Must have disease that can be evaluated according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1)
For trastuzumab pre-treated patients, must have failed prior trastuzumab treatment
Investigator-confirmed diagnosis of Inflammatory Breast Cancer
Must have biopsiable disease

Exclusion criteria:

Prior treatment with HER2-targeted small molecules or antibodies other than trastuzumab (which must have been given in the trastuzumab-failure study population)
Must not have received prior vinorelbine treatment

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Afatinib once daily (OD)

Arm Description

Patients receive afatinib monotherapy once daily until progression of their disease

Outcomes

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).

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).

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).

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).

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).

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 ).

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

Part A: Duration of Unconfirmed Objective Response.

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.

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.

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.

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.

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

Full Information

NCT ID

NCT01325428

First Posted

March 28, 2011

Last Updated

June 17, 2016

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01325428

Brief Title

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

Official Title

An Open Label, Phase II Trial of Afatinib With or Without Vinorelbine for the Treatment of HER2-overexpressing Inflammatory Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Afatinib once daily (OD)

Arm Type

Experimental

Arm Description

Patients receive afatinib monotherapy once daily until progression of their disease

Intervention Type

Drug

Intervention Name(s)

Afatinib once daily (OD)

Intervention Description

Patient to receive afatinib monotherapy until progression of their disease

Intervention Type

Drug

Intervention Name(s)

Vinorelbine Weekly

Intervention Description

Patients additionally receive vinorelbine weekly on disease progression on afatinib monotherapy

Primary Outcome Measure Information:

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.

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.

Secondary Outcome Measure Information:

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.

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.

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.

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.

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.

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.

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.

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.

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.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion criteria: Female patients >=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer Locally advanced or metastatic disease Must have disease that can be evaluated according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1) For trastuzumab pre-treated patients, must have failed prior trastuzumab treatment Investigator-confirmed diagnosis of Inflammatory Breast Cancer Must have biopsiable disease Exclusion criteria: Prior treatment with HER2-targeted small molecules or antibodies other than trastuzumab (which must have been given in the trastuzumab-failure study population) Must not have received prior vinorelbine treatment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

1200.89.10001 Boehringer Ingelheim Investigational Site

City

Los Angeles

State/Province

California

Country

United States

Facility Name

1200.89.10005 Boehringer Ingelheim Investigational Site

City

Durham

State/Province

North Carolina

Country

United States

Facility Name

1200.89.61002 Boehringer Ingelheim Investigational Site

City

East Bentleigh

State/Province

Victoria

Country

Australia

Facility Name

1200.89.61003 Boehringer Ingelheim Investigational Site

City

Perth

State/Province

Western Australia

Country

Australia

Facility Name

1200.89.85201 Boehringer Ingelheim Investigational Site

City

Hong Kong

Country

Hong Kong

Facility Name

1200.89.82001 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1200.89.82002 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1200.89.66002 Boehringer Ingelheim Investigational Site

City

Bangkok

Country

Thailand

Facility Name

1200.89.66004 Boehringer Ingelheim Investigational Site

City

Bangkok

Country

Thailand

Facility Name

1200.89.66003 Boehringer Ingelheim Investigational Site

City

Chiangmai

Country

Thailand

Facility Name

1200.89.66001 Boehringer Ingelheim Investigational Site

City

Hat-Yai, Songkhla

Country

Thailand

Facility Name

1200.89.21601 Boehringer Ingelheim Investigational Site

City

Ariana

Country

Tunisia

Facility Name

1200.89.21602 Boehringer Ingelheim Investigational Site

City

Sousse

Country

Tunisia

Facility Name

1200.89.44002 Boehringer Ingelheim Investigational Site

City

Bournemouth

Country

United Kingdom

Facility Name

1200.89.44001 Boehringer Ingelheim Investigational Site

City

London

Country

United Kingdom

Facility Name

1200.89.44003 Boehringer Ingelheim Investigational Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

27923043

Citation

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.

Results Reference

derived

Links:

URL

http://trials.boehringer-ingelheim.com/

Description

Related Info

Breast Neoplasms

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial