BIBW 2992 (Afatinib) for the Treatment of Patients With HER2-positive, Hormone-refractory Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01320280
First received: March 17, 2011
Last updated: April 7, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to find out what effects, good and/or bad, BIBW 2992 (Afatinib) has on patients and their advanced prostate cancer which does not respond to hormone or chemotherapy any more. Only patients with tumors which have an increased amounts of a protein called HER2 on their cell surface will be included.

BIBW 2992 (Afatinib) is a drug which in advanced clinical testing in lung and breast cancer.


Condition Intervention Phase
Refractory Cancer
Drug: BIBW 2992 (Afatinib)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single-arm, Open-label, Single-center Phase II Study Evaluating the Efficacy and Safety of BIBW 2992 (Afatinib) for the Treatment of Patients With HER2-positive, Hormone-refractory Prostate Cancer After Failure of Treatment With Docetaxel or Ineligible for Treatment With Docetaxel

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • Objective PSA responses according to Bubley criteria [ Time Frame: every two months ] [ Designated as safety issue: No ]
    Bubley criteria see Bubley GJ, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol 1999; 17: 3461-3467


Secondary Outcome Measures:
  • Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) [ Time Frame: every 2 months ] [ Designated as safety issue: No ]
  • Duration of PSA-response (Bubley criteria) or objective responses [ Time Frame: every 2 months ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
    Description AEs according to CTC criteria


Enrollment: 29
Study Start Date: May 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992 (Afatinib)
BIBW 2992 (Afatinib) 50mg daily continuously (oral medication)
Drug: BIBW 2992 (Afatinib)
50 mg BIBW 2992 (Afatinib) tablets daily continuously

Detailed Description:

This is a phase II study of BIBW 2992 (Afatinib) in patients with hormone and chemotherapy (docetaxel) refractory, HER2 overexpressing prostate cancer. The exploratory study following a two stage Gehan design. In the first stage 29 patients with be treated. Additional patients will be recruited in a second stage depending on the number of responding patients in the first step. Patients will receive BIBW 2992 (Afatinib) orally at a dose of 50 mg daily. Response to therapy will be scored according to PSA values (Bubley criteria) and to CT scans (RECIST criteria). Patients will be seen at 2 or 4 weeks intervals by a medical professional while on the medication for toxicity assessment and physical examination. Disease evaluations will occur at baseline and every 2 months thereafter. These evaluations will include PSA testing and CT Scans (if appropriate).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

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) 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
  • Any contraindications for therapy with BIBW 2992.
  • Known hypersensitivity to BIBW 2992.
  • Use of any investigational drug within 4 weeks of start of treatment
  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: NCT01320280

Locations
Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Boehringer Ingelheim
Investigators
Principal Investigator: Walter Fiedler, M.D: Universitätsklinikum Hamburg-Eppendorf
  More Information

Publications:
Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01320280     History of Changes
Other Study ID Numbers: 1200.138
Study First Received: March 17, 2011
Last Updated: April 7, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
Prostate cancer, BIBW 2992 (Afatinib) , HER inhibitor

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on July 24, 2014