Study to evaluate the efficacy and safety of the trial substance BIBW 2992 (Afatinib) for treatment of patients with prostate cancer after failure of treatment with docetaxel or ineligible for treatment with docetaxel

Conditions: Patients with HER2-positive, hormone-refractory prostate cancer after failure of treatment with docetaxel or ineligible for treatment with docetaxel.
MedDRA version: 13.1Level: LLTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Body processes [G] - Cell Physiological Phenomena [G04]

Registration Number: EUCTR2010-024164-18-DE

Lead Sponsor: niversity Medical Center Hamburg-Eppendorf

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: Not specified

Inclusion Criteria

•Patients must provide written informed consent
•Age = 18 years
•Patients must have histological proven, hormone-refractory prostate cancer
•Patients must have failed prior therapy with docetaxel or must be ineligible for treatment with docetaxel
•Patients must have ECOG performance status = 2
•Patients must not have received any prior therapy targeting EGFR or HER2
•Patients must have adequate bone marrow, renal and hepatic function
•Patients must not have a history of severe heart disease
•Patients must not have had a myocardial infarction within the previous six months
•Patients must have normal left ventricular ejection fraction (LVEF = normal limit of institution)
•Patients must not have symptomatic brain or leptomeningeal metastatic disease
•Patients must have recovered from previous treatment-related adverse effects to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) grade = 1

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 37

Exclusion Criteria

•Prior treatment with EGFR/HER2-targeted small molecules or antibodies, i.e. trastuzumab and/or lapatinib
•Known pre-existing interstitial lung disease
•Radiotherapy, chemotherapy, hormone therapy (with the exception of GnRH agonists), immunotherapy or surgery (other than biopsy) within 4 weeks prior to start of treatment with BIBW2992. GnRH-agonists are allowed at the discretion of the investigator.
•Active brain metastases (defined as stable for < 4 weeks and/or symptomatic and/or requiring changes of treatment with anticonvulsants or steroids within the past 4 weeks and/or leptomeningeal disease). Patients with known history of brain metastases should undergo a baseline brain image to ensure that the disease is stable.
•Any other current malignancy or malignancy diagnosed within the past five (5) years (other than non-melanomatous skin cancer).
•Significant 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.
•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 randomisation.
•Cardiac left ventricular function with resting ejection fraction of less than 50%.
•Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient’s safety or interfere with the evaluation of the safety of the test drug.
•Absolute neutrophil count (ANC) < 1500 / mm³.
•Platelet count < 75,000 / mm³
•Calculated creatinine clearance < 60 ml / min (using Cockcroft-Gault formula for GFR estimate, see appendix 1) or serum creatinine > 1.5 times upper limit of normal.
•Uncontrolled hypercalcemia
•Patients unable to comply with the protocol.
•Known hepatitis B infection, known hepatitis C infection or known HIV carrier.
•Known or suspected active drug or alcohol abuse.
•Requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2.1 of the protocol.
•Any contraindications for therapy with BIBW 2992.
•Known hypersensitivity to BIBW 2992.
•Use of any investigational drug within 4 weeks of start of treatment.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of the trial is to evaluate the efficacy and safety of BIBW 2992 in this patient population. If this study shows promising results, further studies to evaluate the benefit of BIBW 2992 in this subgroup of HER2-positive patients with hormone-refractory prostate cancer are warranted.;Secondary Objective: none;Primary end point(s): PSA response rate according to Bubley criteria of BIBW 2992 in patients with hormone refractory prostate cancer after failure of docetaxel chemotherapy. ;Timepoint(s) of evaluation of this end point: PSA should be determined at screening, visit 1 of every other cycle, EOT, and Follow-up 1.

Secondary Outcome Measures