Afatinib alone or in combination with vinorelbine in patients with HER2 positive breast cancer suffering from brain metastases

• Conditions: HER2 positive breast cancer with progressive brain metastases after trastuzumab or lapatinib based therapy; MedDRA version: 14.1Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-021415-16-IT
• Lead Sponsor: BOEHRINGER ING.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-02
• Last Update Posted: 14 September 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 152

Inclusion Criteria

1.Written informed consent that is consistent with ICH-GCP guidelines and local legislation. 2.Life expectancy of at least three (3) months in the investigator's opinion. 3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1 or 2. 4.Female patients >=18 years 5.Histologically confirmed diagnosis of HER2-overexpressing breast cancer (HER2 status as previously assessed by local lab is acceptable). 6. Documented CNS recurrence/progression (by imaging) during or after a HER2 inhibitor (Trastuzumab or Lapatinib) based therapy (no leptomeningeal carcinomatosis as the only site of CNS metastases) 7.At least one measurable and progressive lesion in the CNS (>=10 mm on T1-weighted, gadolinium-enhanced MRI) after prior systemic and/or radiation therapy. Measurable or non-measurable extra cranial metastases allowed. 8.Previous treatment with HER2 inhibitors (trastuzumab or lapatinib) to be discontinued prior to first study drug administration (at least 14 days for trastuzumab and other antibodies, at least 7 days for lapatinib). 9.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 drug administration. 10.Patients must have recovered to baseline condition or to CTCAE v. 3.0 grade <= 1 from any acute CTCAE v. 3.0 grade >=2 side effects of previous treatments. 11.Prior surgery, whole brain radiotherapy or stereotactic radiosurgery are 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. 12.At least 2 weeks since prior radiotherapy or stereotactic radiosurgery and 4 weeks since prior surgery.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 122
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.Prior treatment with HER2-targeted treatment other than lapatinib and trastuzumab 2.Requirement for treatment with any of the prohibited concomitant medications listed in Section 4.2.2 (restrictions) or in the product SPC of the control arm treatment. 3.Known pre-existing interstitial lung disease. 4.Any other current malignancy or malignancy diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer). 5.Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade >=2 diarrhoea of any aetiology. 6. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension (investigator's assessment), congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia in the investigator's opinion. 7.Cardiac left ventricular function by echocardiogram or MUGA scan with resting ejection fraction of less than 50%. 8.Myocardial infarction within 6 months prior to the first dose of afatinib. 9.Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug. 10.Absolute neutrophil count (ANC) < 1.5 x 10**9/L. 11.Platelet count < 100 x 10**9/L 12.Calculated Creatinine clearance < 60 ml / min (Cockcroft formula – Appendix 1) and serum creatinine > 1.5 times upper limit of normal. 13.Bilirubin > 1.5 times upper limit of normal. 14.Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 3 times the upper limit of normal (ULN) (if related to liver metastases > 5 times ULN). 15.Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial. Acceptable methods of contraception include surgical sterilisation and double barrier method. Double barrier method of contraception is defined as two barrier methods used simultaneously each time the patient has intercourse. Accepted barrier methods include diaphragm, female condom, cervical cap, male condom and intra-uterine device (female and male condom, diaphragm and cervical cap must be used in conjunction with spermicidal jelly/cream). Partner vasectomy, natural ''rhythm'' and spermicidal jelly/cream are not acceptable methods of contraception. 16.Pregnancy or breast-feeding (lactation). 17.Patients unable to comply with the protocol in the investigator’s opinion. 18.Known hepatitis B infection, known hepatitis C infection or known HIV carrier. 19.Known or suspected active drug or alcohol abuse in the investigator's opinion. 20.Any contraindication to treatment with vinorelbine. 21.Known hypersensitivity to afatinib or to vinorelbine, or to the excipients of any of the trial drugs. 22. Treatment with an investigational drug within 2 weeks of the first study drug administration or concurrent participation in another clinical trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified