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

NCT01320280 | Terminated Phase 2

• 1 other identifier: 1200.138
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Refractory Cancer

Keywords

Prostate cancer, BIBW 2992 (Afatinib) , HER inhibitor

Outcome Measures

Primary Outcomes (1)

• Objective PSA responses according to Bubley criteria

  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

  every two months

Secondary Outcomes (3)

• Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

  every 2 months

• Duration of PSA-response (Bubley criteria) or objective responses

  every 2 months

• Safety

  every 4 weeks

Study Arms (1)

BIBW 2992 (Afatinib)

EXPERIMENTAL

BIBW 2992 (Afatinib) 50mg daily continuously (oral medication)

Drug: BIBW 2992 (Afatinib)

Interventions

BIBW 2992 (Afatinib) DRUG

50 mg BIBW 2992 (Afatinib) tablets daily continuously

BIBW 2992 (Afatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Related Publications (2)

• Yap TA, Vidal L, Adam J, Stephens P, Spicer J, Shaw H, Ang J, Temple G, Bell S, Shahidi M, Uttenreuther-Fischer M, Stopfer P, Futreal A, Calvert H, de Bono JS, Plummer R. Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol. 2010 Sep 1;28(25):3965-72. doi: 10.1200/JCO.2009.26.7278. Epub 2010 Aug 2.

  PMID: 20679611 BACKGROUND

• Minner S, Jessen B, Stiedenroth L, Burandt E, Kollermann J, Mirlacher M, Erbersdobler A, Eichelberg C, Fisch M, Brummendorf TH, Bokemeyer C, Simon R, Steuber T, Graefen M, Huland H, Sauter G, Schlomm T. Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res. 2010 Mar 1;16(5):1553-60. doi: 10.1158/1078-0432.CCR-09-2546. Epub 2010 Feb 23.

  PMID: 20179235 RESULT

MeSH Terms

Conditions

Neoplasms; Prostatic Neoplasms

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Walter Fiedler, M.D:

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 22, 2011
• Study Start: May 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: July 1, 2022

Record last verified: 2022-06

Locations

DE (1)