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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01441596
First received: September 26, 2011
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Breast Neoplasms
Neoplasm Metastasis
Drug: Vinorelbine
Drug: Investigator's choice of treatment
Drug: afatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2011
Estimated Study Completion Date: September 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
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.
Drug: Vinorelbine
Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
Drug: afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441596

  Show 40 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01441596     History of Changes
Other Study ID Numbers: 1200.67, 2010-021415-16
Study First Received: September 26, 2011
Last Updated: July 9, 2014
Health Authority: Canada: Health Canada
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Vinorelbine
Vinblastine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014