Lux-Breast 3; Afatinib Alone or in Combination With Vinorelbine in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Suffering From Brain Metastases

• ClinicalTrials.gov Identifier: NCT01441596
• Recruitment Status: Completed
• First Posted: September 27, 2011
• Results First Posted: February 25, 2015
• Last Update Posted: September 7, 2015
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: September 26, 2011
• First Posted Date: September 27, 2011
• Results First Submitted Date: February 10, 2015
• Results First Posted Date: February 25, 2015
• Last Update Posted Date: September 7, 2015
• Study Start Date: October 2011
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 25, 2015)

Patient Benefit Rate at 12 Weeks [ Time Frame: 12 weeks from randomisation ]

Percentage of patients with patient benefit at week 12. Patient benefit was defined by the absence of central nervous system (CNS) disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in addition to no tumour-related worsening of the neurological signs and symptoms (NSS), no tumour-related increase in corticosteroid dosage and no progression of extra CNS disease according to RECIST 1.1

• Original Primary Outcome Measures (submitted: September 26, 2011): Patient benefit at 12 weeks defined as absence of CNS or extra CNS progression (RECIST 1.1) and no tumour related worsening of the neurological signs and symptoms or corticosteroid dosage [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: August 25, 2015)

• Progression-Free Survival [ Time Frame: From first drug administration until 28 days after end of treatment, up to 805 days ]
  Progression-Free Survival is defined as the time from the date of randomisation to the date of disease progression or death whichever came first. Disease progression was defined as either disease progression in CNS lesions (including worsening in NSS and use of corticosteroid) or disease progression in extra-CNS lesions according to RECIST 1.1.
• Overall Survival [ Time Frame: From first drug administration until 28 days after end of treatment, up to 805 days ]
  Overall Survival is defined as time from randomisation to the date of death from any cause.

Original Secondary Outcome Measures (submitted: September 26, 2011)

• Progression-Free Survival [ Time Frame: 6 months ]
• Overall Survival [ Time Frame: 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lux-Breast 3; Afatinib Alone or in Combination With Vinorelbine in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Suffering From Brain Metastases
• Official Title: Lux-Breast 3; Randomised Phase II Study of Afatinib Alone or in Combination With Vinorelbine Versus Investigator's Choice of Treatment in Patients With HER2 Positive Breast Cancer With Progressive Brain Metastases After Trastuzumab and/or Lapatinib Based Therapy
• Brief Summary: The aim of this study is to investigate the efficacy and safety of afatinib alone or in combination with vinorelbine, as treatment in patients with HER2-overexpressing metastatic breast cancer, who have progressive brain lesions after trastuzumab and/or lapatinib based therapy
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Neoplasms
• Neoplasm Metastasis

Intervention

• Drug: Vinorelbine
  Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
• Drug: Investigator's choice of treatment
  Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines.
• Drug: afatinib
  Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.

Study Arms

• Experimental: arm A: Afatinib monotherapy
  Afatinib monotherapy: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
  Intervention: Drug: afatinib
• Experimental: arm B: Afatinib in combination with vino
  Afatinib 40 mg per day, continuous treatment, in combination with vinorelbine Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course.
  Interventions:

  • Drug: Vinorelbine
  • Drug: afatinib
• Active Comparator: arm C: investigator's choice of treatmen
  Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines.
  Intervention: Drug: Investigator's choice of treatment

• Publications *: Cortes J, Dieras V, Ro J, Barriere J, Bachelot T, Hurvitz S, Le Rhun E, Espie M, Kim SB, Schneeweiss A, Sohn JH, Nabholtz JM, Kellokumpu-Lehtinen PL, Taguchi J, Piacentini F, Ciruelos E, Bono P, Ould-Kaci M, Roux F, Joensuu H. Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial. Lancet Oncol. 2015 Dec;16(16):1700-10. doi: 10.1016/S1470-2045(15)00373-3. Epub 2015 Nov 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2014): 121
• Original Estimated Enrollment (submitted: September 26, 2011): 120
• Actual Study Completion Date: August 2014
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

1. patients with HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after a HER2 inhibitor (Trastuzumab and/or Lapatinib) based therapy (no leptomeningeal carcinomatosis as the only site of CNS metastases)
2. at least one measurable and progressive lesion in the brain (=10 mm on T1-weighted, gadolinium-enhanced Magnetic Resonance Imaging). Measurable or non measurable extracranial metastases allowed.
3. previous treatment with HER2 inhibitors to be discontinued prior to first study treatment administration (at least 14 days for trastuzumab and other antibodies, at least 7 days for lapatinib).
4. previous chemotherapy and hormonal therapy (adjuvant and metastatic regimens) allowed, but chemotherapy must have been discontinued at least 14 days and hormonal therapy at least 7 days prior to first study treatment administration.
5. Patients must have recovered to baseline condition or to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade = 1 from any acute CTCAE v. 3.0 grade =2 side effects of previous treatments.
6. prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed provided that there is unequivocal evidence of one or more new and/or progressive brain metastases after completion of whole brain radiotherapy or stereotactic radiosurgery.

Exclusion criteria:

1. Prior treatment with HER2- tyrosine kinase inhibitor other than lapatinib
2. Any other current malignancy or malignancy diagnosed within the past five (5) years (other than bilateral primary breast cancer, metastases to the contralateral breast, non-melanomatous skin cancer and in situ cervical cancer).
3. Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or Common Terminology Criteria (CTC) grade =2 diarrhoea of any aetiology.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Finland, France, Germany, Italy, Korea, Republic of, Spain, United States
• Removed Location Countries: El Salvador

Administrative Information

• NCT Number: NCT01441596
• Other Study ID Numbers: 1200.67; 2010-021415-16 ( EudraCT Number: EudraCT )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: August 2015