Breast Neoplasms
Conditions
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.
Interventions
DRUGAfatinib once daily (OD)
Patient to receive afatinib monotherapy until progression of their disease
DRUGVinorelbine Weekly
Patients additionally receive vinorelbine weekly on disease progression on afatinib monotherapy
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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)). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
Countries
Australia, Hong Kong, South Korea, Thailand, Tunisia, United Kingdom, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Afatinib Once Daily. Part B: Afatinib+V (Vinorelbine). 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. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part A | Clinical signs, symptoms of progression | 2 |
| Part A | Other adverse event | 1 |
| Part A | Other reason not defined above | 2 |
| Part A | Progressive disease according to RECIST | 9 |
| Part A | Refused continue taking trial medication | 2 |
| Part B | Other reason not defined above | 1 |
| Part B | Refused continue taking trial medication | 2 |
Baseline characteristics
| Characteristic | Part A: Afatinib Once Daily. Part B: Afatinib+V (Vinorelbine). |
|---|---|
| Age, Customized Part A | 51.5 Years STANDARD_DEVIATION 8.8 |
| Age, Customized Part B | 51.5 Years STANDARD_DEVIATION 12.5 |
| Sex/Gender, Customized Female (Part A) | 26 Participants |
| Sex/Gender, Customized Female (Part B) | 10 Participants |
| Sex/Gender, Customized Male (Part A) | 0 Participants |
| Sex/Gender, Customized Male (Part B) | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 10 / 10 |
| serious Total, serious adverse events | 12 / 26 | 4 / 10 |
Outcome results
Primary
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).
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.
Population: TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | 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). | 35 Percentage of participants |
Primary
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).
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.
Population: TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | 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). | 20 Percentage of participants |
Secondary
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.
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.
Population: TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part A: Confirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1). | 31 Percentage of participants |
Secondary
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)).
Time frame: From first drug administration until end of Part A, up to 929 days.
Population: TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part A: Duration of Unconfirmed Objective Response. | NA Days |
Secondary
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.
Time frame: From first drug administration until end of Part A, up to 713 days.
Population: TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part A: Progression Free Survival. | 110.5 Days |
Secondary
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.
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.
Population: TRT A Treated Set (Part A): All patients who were documented to have taken at least one dose of Afatinib in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part A: Unconfirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1). | 42 Percentage of participants |
Secondary
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.
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.
Population: TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part B: Confirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1). | 10 Percentage of participants |
Secondary
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).
Time frame: From first drug administration until end of Part B, up to 929 days.
Population: TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part B: Duration of Unconfirmed Objective Response. | 57 Days |
Secondary
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.
Time frame: From first drug administration until end of Part B, up to 230 days.
Population: TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part B: Progression Free Survival. | 106.0 Days |
Secondary
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.
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.
Population: TRT B Treated set (Part B): All patients who received at least one dose each of Afatinib and Vinorelbine in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Part B: Unconfirmed Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST 1.1 ). | 30 Percentage of participants |
Secondary
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.
Time frame: From first drug administration until end of study, up to 700 days.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Afatinib Once Daily (OD). | Progression Free Survival Over the Whole Sudy. | 253.0 Days |