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

NCT01271725 | Completed Phase 2 Results

• 2 other identifiers: 1200.982010-021945-29
• Study Type: interventional
• Target: 74
• Locations: 6 countries
• Sites: 27

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

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Best Overall Response According to RECIST v1.1 (With Confirmation)

  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)

  From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

• Progression Free Survival (PFS)

  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

  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

  From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days

Study Arms (3)

Afatinib 40mg once daily (OD)

EXPERIMENTAL

Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease

Drug: Afatinib 40mg once daily (OD)

Paclitaxel 80 mg/m2 weekly

EXPERIMENTAL

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

Vinorelbine 25 mg/m2 weekly

EXPERIMENTAL

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

Interventions

Vinorelbine 25 mg/m2 weekly DRUG

Patients to additionally receive vinorelbine at a dose of 25 mg/m2 weekly on disease progression on afatinib monotherapy

Vinorelbine 25 mg/m2 weekly

Afatinib 40mg once daily (OD) DRUG

Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease

Afatinib 40mg once daily (OD)

Paclitaxel 80 mg/m2 weekly DRUG

Patients to additionally receive paclitaxel at a dose of 80 mg/m2 weekly on disease progression on afatinib monotherapy

Paclitaxel 80 mg/m2 weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients \>=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer
• Stage IV metastatic disease
• 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
• Must have failed or progressed on either trastuzumab or lapatinib or trastuzumab and lapatinib treatment in the neoadjuvant and/or adjuvant setting

You may not qualify if:

• Prior first line therapy for metastatic breast cancer
• Known pre-existing interstitial lung disease
• Active brain metastases
• 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.
• Cardiac left ventricular function with resting ejection fraction of less than 50%.
• 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
• Prior treatment with paclitaxel in the past 12 months

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (27)

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Sujan Surgical Cancer Hospital

Amravati, 444606, India

Location

Tata Memorial Hospital

Maharashtra, 400 012, India

Location

Curie Manavata Cancer Centre

Maharashtra, 422 004, India

Location

Central India Cancer Research Institute

Nagpur, 440010, India

Location

Ruby Hall Clinic

Pune, 411001, India

Location

Regional Cancer Center

Thiruvananthapuram, 695 011, India

Location

University Clinical Center, Gdansk

Gdansk, 80-211, Poland

Location

St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"

Kazan', 420029, Russia

Location

Clinical Oncology Dispensary No. 1, Dept. Chemotherapy

Krasnodar, 350040, Russia

Location

N.A. Semashko Central Clinical Hospital, Moscow

Moscow, 129128, Russia

Location

SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"

Pyatigorsk, 357502, Russia

Location

SBIH "Samara Regional Clinical Oncol. Dispensary", Samara

Samara, 443 031, Russia

Location

GUZ "Oncological Dispesary #2"

Sochi, 354057, Russia

Location

Stavropol Regional Clin. Oncology Dispensary Dept. Oncology

Stavropol, 355 047, Russia

Location

Yaroslavl Regional Clinical Oncology Hosp. Dept.Chemotherapy

Yaroslavl, 150 040, Russia

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

Koo Foundation Sun Yet-Sen Cancer Center

Taipei, 112, Taiwan

Location

Taipe Veterans General Hospital

Taipei, 112, Taiwan

Location

North Devon District Hospital

Barnstaple, EX31 4JB, United Kingdom

Location

Royal Bournemouth and Christchurch Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35138529 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vinorelbine; Afatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Amides; Organic Chemicals; Quinazolines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

Enrollment of patients into the afatinib and vinorelbine combination option was stopped prematurely following a benefit-risk analysis in other trial. Any patients who were already benefiting from this combination were allowed to continue.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2011
• First Posted: January 7, 2011
• Study Start: May 24, 2011
• Primary Completion: March 13, 2017
• Study Completion: March 13, 2017
• Last Updated: June 17, 2019
• Results First Posted: June 17, 2019

Record last verified: 2019-03

Locations

HK (2); IN (6); RU (8); TW (6); PL (1); GB (4)