Clinical trial NCT01271725: LUX-Breast 2; Afatinib in HER2 (Human Epidermal Growth Factor Receptor)-Treatment Failures
Official title: LUX-Breast 2; An Open Label, Phase II Trial of Afatinib (BIBW 2992) in Patients With Metastatic HER2-overexpressing Breast Cancer Failing HER2-targeted Treatment in the Neoadjuvant and/or Adjuvant Treatment Setting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-01-07
Enrollment: 74
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The general aim of this study is to investigate the efficacy and safety of afatinib (BIBW 2992) alone and in combination with weekly paclitaxel or weekly vinorelbine (in patients who progress on afatinib monotherapy within this trial) as treatment in patients with HER2-overexpressing, metastatic breast cancer, who failed HER2-targeted treatment in the neoadjuvant or adjuvant setting


Eligibility criteria: Inclusion criteria:

1. Female patients \>=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer
2. Stage IV metastatic disease
3. At least one measurable lesion according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1). Skin, bone and brain lesions are considered non-target lesions
4. Must have failed or progressed on either trastuzumab or lapatinib or trastuzumab and lapatinib treatment in the neoadjuvant and/or adjuvant setting

Exclusion criteria:

1. Prior first line therapy for metastatic breast cancer
2. Known pre-existing interstitial lung disease
3. Active brain metastases
4. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to trial treatment.
5. Cardiac left ventricular function with resting ejection fraction of less than 50%.
6. Prior treatment with Epidermal Growth Factor Receptor (EGFR)/HER2-targeted small molecules or antibodies other than trastuzumab and lapatinib in the neoadjuvant or adjuvant setting
7. Prior treatment with paclitaxel in the past 12 months
8. Must not have received prior vinorelbine treatment - Further exclusion criteria apply

Primary outcomes:
measure: Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1
timeFrame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Secondary outcomes:
measure: Best Overall Response According to RECIST v1.1 (With Confirmation)
timeFrame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
measure: Best Overall Response According to RECIST v1.1 (Regardless of Confirmation)
timeFrame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
measure: Progression Free Survival (PFS)
timeFrame: From drug start date in monotherapy to 1st disease progression and drug start date in combination therapy to 2nd disease progression
measure: Duration of Objective Response According to RECIST v1.1
timeFrame: From the first objective response to the time of progression or death, up to 1562 days
measure: Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher
timeFrame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
measure: Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP)
timeFrame: Baseline and End of treatment period, up to 1562 days
measure: Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP)
timeFrame: Baseline and End of treatment period, up to 1562 days
measure: Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values
timeFrame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Amravati
country: India
facility: Sujan Surgical Cancer Hospital
city: Maharashtra
country: India
facility: Tata Memorial Hospital
city: Maharashtra
country: India
facility: Curie Manavata Cancer Centre
city: Nagpur
country: India
facility: Central India Cancer Research Institute
city: Pune
country: India
facility: Ruby Hall Clinic
city: Thiruvananthapuram
country: India
facility: Regional Cancer Center
city: Gdansk
country: Poland
facility: University Clinical Center, Gdansk
city: Kazan
country: Russian Federation
facility: St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Dispensary No. 1, Dept. Chemotherapy
city: Moscow
country: Russian Federation
facility: N.A. Semashko Central Clinical Hospital, Moscow
city: Pyatigorsk
country: Russian Federation
facility: SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"
city: Samara
country: Russian Federation
facility: SBIH "Samara Regional Clinical Oncol. Dispensary", Samara
city: Sochi
country: Russian Federation
facility: GUZ "Oncological Dispesary #2"
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Clin. Oncology Dispensary Dept. Oncology
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Oncology Hosp. Dept.Chemotherapy
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yet-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Taipe Veterans General Hospital
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth and Christchurch Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Hickish T, Mehta A, Liu MC, Huang CS, Arora RS, Chang YC, Yang Y, Vladimirov V, Jain M, Tsang J, Pemberton K, Sadrolhefazi B, Jin X, Tseng LM. Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): an open-label, multicenter, phase II trial. Breast Cancer Res Treat. 2022 Apr;192(3):593-602. doi: 10.1007/s10549-021-06449-4. Epub 2022 Feb 9.