LUX-Breast 2; Afatinib in HER2 (Human Epidermal Growth Factor Receptor)-Treatment Failures

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

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

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Afatinib 40mg once daily (OD); Drug: Paclitaxel 80 mg/m2 weekly; Drug: Vinorelbine 25 mg/m2 weekly

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• India
  • Amravati, India, 444606
    • Sujan Surgical Cancer Hospital
  • Maharashtra, India, 422 004
    • Curie Manavata Cancer Centre
  • Maharashtra, India, 400 012
    • Tata Memorial Hospital
  • Nagpur, India, 440010
    • Central India Cancer Research Institute
  • Pune, India, 411001
    • Ruby Hall Clinic
  • Thiruvananthapuram, India, 695 011
    • Regional Cancer Center
• Poland
  • Gdansk, Poland, 80-211
    • University Clinical Center, Gdansk
• Russian Federation
  • Kazan, Russian Federation, 420029
    • St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
  • Krasnodar, Russian Federation, 350040
    • Clinical Oncology Dispensary No. 1, Dept. Chemotherapy
  • Moscow, Russian Federation, 129128
    • N.A. Semashko Central Clinical Hospital, Moscow
  • Pyatigorsk, Russian Federation, 357502
    • SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"
  • Samara, Russian Federation, 443 031
    • SBIH "Samara Regional Clinical Oncol. Dispensary", Samara
  • Sochi, Russian Federation, 354057
    • GUZ "Oncological Dispesary #2"
  • Stavropol, Russian Federation, 355 047
    • Stavropol Regional Clin. Oncology Dispensary Dept. Oncology
  • Yaroslavl, Russian Federation, 150 040
    • Yaroslavl Regional Clinical Oncology Hosp. Dept.Chemotherapy
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 112
    • Taipe Veterans General Hospital
  • Taipei, Taiwan, 112
    • Koo Foundation Sun Yet-Sen Cancer Center
• United Kingdom
  • Barnstaple, United Kingdom, EX31 4JB
    • North Devon District Hospital
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth and Christchurch Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afatinib 40mg once daily (OD); Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease	Drug: Afatinib 40mg once daily (OD); Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease
Experimental: Paclitaxel 80 mg/m2 weekly; Patients to additionally receive paclitaxel at a dose of 80 mg/m2 weekly on disease progression on afatinib monotherapy	Drug: Paclitaxel 80 mg/m2 weekly; Patients to additionally receive paclitaxel at a dose of 80 mg/m2 weekly on disease progression on afatinib monotherapy
Experimental: Vinorelbine 25 mg/m2 weekly; Patients to additionally receive vinorelbine at a dose of 25 mg/m2 weekly on disease progression on afatinib monotherapy	Drug: Vinorelbine 25 mg/m2 weekly; Patients to additionally receive vinorelbine at a dose of 25 mg/m2 weekly on disease progression on afatinib monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1	Objective response according to RECIST v1.1. Best overall response of confirmed complete response (CR) or confirmed partial response (PR) recorded since first administration of trial medication and until the earliest of disease progression, death or start of next treatment in each part separately. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of participants with OR along with exact 95% Confidence Interval by Clopper and Pearson is presented.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response According to RECIST v1.1 (With Confirmation)	Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Best Overall Response According to RECIST v1.1 (Regardless of Confirmation)	Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part (without clinical disease assessment) .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Progression Free Survival (PFS)	Progression Free Survival is defined as the time from the drug start date to the date of 1st disease progression or death for monotherapy and 2nd disease progression or death from the drug start date of the combination therapy for combination therapy'. Median is calculated from the Kaplan-Meier curve.	From drug start date in monotherapy to 1st disease progression and drug start date in combination therapy to 2nd disease progression
Duration of Objective Response According to RECIST v1.1	Duration of objective response, defined as the time from first objective response to the time of progression or death. (regardless of confirmation). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	From the first objective response to the time of progression or death, up to 1562 days
Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher	Percentage of patients with highest common terminology criteria for adverse events (CTCAE) version 3.0 Grade of 3 or higher.	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP)	Change from baseline to end of treatment in systolic blood pressure (SBP).	Baseline and End of treatment period, up to 1562 days
Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP)	Change from baseline to end of treatment in diastolic blood pressure (DBP).	Baseline and End of treatment period, up to 1562 days
Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values	Number of patient with possibly clinically significant (PCS) laboratory values by functional group (haematology, differentials, coagulation, electrolytes, enzymes, and substrates). Acronyms Used: Prothrombin time-International normalized ratio (PT-INR), Alanine aminotransferase/Glutamic pyruvic transaminase (ALT/GPT) Serum glutamic pyruvic transaminase (SGPT), Aspartate aminotransferase/Glutamic-oxaloacetic transaminase (AST/GOT) Serum glutamic-oxaloacetic transaminase (SGOT)	From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2011
• Primary Completion (Actual): March 13, 2017
• Study Completion (Actual): March 13, 2017

Study Registration Dates

• First Submitted: January 6, 2011
• First Submitted That Met QC Criteria: January 6, 2011
• First Posted (Estimate): January 7, 2011

Study Record Updates

• Last Update Posted (Actual): June 17, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Vinorelbine; Afatinib
• Other Study ID Numbers: 1200.98; 2010-021945-29 (EudraCT Number)