Trial document

drksid header


Trial Description

start of 1:1-Block title


A phase II trial to evaluate safety and efficacy of combined trastuzumab and AUY922 in advanced non-small cell lung cancer (NSCLC) with HER2 - overexpression or -amplification or - mutation.

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym


end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial


end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

The main aim of the trial is to evaluate the efficasy and the safety of AUY 922 + Herceptin (in combination). Both medication should block cancer cells growing. Herceptin blocks especially cancer cells with a specific genetic alteration (HER2). Therefore only patients with HER2 alteration in non-small lung cancer can participate in this trial. Herceptin is approved for other diseases. AUY 922 is not approved. The drugs will be given by infusion. During the infusion and after the infusion blood samples will be taken to determine the drug level in the blood.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Trastuzumab and AUY922 in HER2-overexpressed or -amplified or –mutated NSCLC

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003301
  •   2012/11/02
  •   [---]*
  •   yes
  •   Approved
  •   12-114, Ethik-Kommission der Medizinischen Fakultät der Universität zu Köln
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2011-005655-13 
  •   4038232 
  •   TRY  ( Universität Köln)
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   C34 -  Malignant neoplasm of bronchus and lung
  •   HER2-overexpression or -amplification or -mutation
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Part 1: Trastuzumab (Herceptin®) Monotherapy, once weekly. Loading dose 4 mg/ kg, subsequently 2 mg/ kg. In case of progression:
    Part 2: Trastuzumab (Herceptin ®) once weekly, 2 mg/ kg + AUY922 once weekly, 70 mg/m2 - until progression.

    Both Infusions are given the same day.
end of 1:N-Block interventions
start of 1:1-Block design


  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
  •   No
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Response rate (RR) of the combination therapy with Trastuzumab and AUY922, determined by CT every 6 weeks

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

• To evaluate the response rate in patients treated with trastuzumab monotherapy by CT (every 6 weeks)
• To evaluate the tolerability of trastuzumab and AUY922 in combination (endpoints: assessment of adverse events (AEs) according to CTC-AE V4.0, ongoing)
• To evaluate the clinical efficacy of trastuzumab monotherapy and the combination descriptively (endpoints: progression-free survival (PFS) determined by CT every 6 weeks, overall survival (OS) determined by contact every 6 months)
• To correlate clinical efficacy of trastuzumab monotherapy and the combination with HER2 overexpression or mutational or amplification status descriptively. Response and HER 2 status will be compared. Her 2 Status will be analyzed before start of study medication
• To assess pharmacokinetics of AUY922 and trastuzumab (PK blood samples will be taken weekly)
• To establish a pharmacokinetic / pharmacodynamic model with regard to response rate and adverse events

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment


  •   Planned
  •   2012/12/01
  •   29
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

• Stage IV NSCLC patients after failure of at least one standard therapy with HER2 protein overexpression or gene amplification (FISH-positive) or mutation
• Age > 18 years
• ECOG performance status 0 to 2
• Life expectancy of at least 12 weeks
• Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
• Adequate bone marrow, liver and renal function and adequate electrolyte balance as assessed by
following laboratory requirements conducted 14 days prior to treatment:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1500 /mm3
• Platelet count ≥ 100,000/µL
• Total bilirubin ≤ 2 x ULN
• ALT, AST and alkaline phosphatase (AP) ≤ 2.5 x ULN or ≤ 5.0 x ULN, if liver metastasis are present
• PT-INR/PTT < 1.5 x ULN
• Creatinine clearence (CrCl) ≥ 60ml/min calculated by either MDRD-formel or by 24 hours urine collection
• Total calcium (corrected for serum albumin) within normal limits or correctable with supplements
• Magnesium within lower normal limits or correctable with supplements
• Potassium within normal limits or correctable with supplements
• Written informed consent (after adequate explanation of the trial) to participate in the trial and to adhere to trial procedures, as well as consenting to data protection procedures
• In case of females with childbearing potential (definition of menopause is no bleeding at least 12 months after last menstruation):
- negative serum pregnancy test in women with childbearing potential
- efective method of contraception (Pearl-Index not greater than 1%)

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

• Known hypersensitivity to any study medication
• Other history of ongoing malignancy that would potentially interfere with the interpretation of efficacy
• Previous treatment with Hsp90 inhibitors (e.g.17-AAG)
• Treatment with therapeutic doses of coumarin derivatives..Low doses of coumarin derivatives (e.g. < 2mg/day) are permitted
• Pregnant or lactating women
• Patients with concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes mellitus, active untreated of uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol
• Impaired cardiac function including any of the following:
o History (or family history) of long QT syndrome
o Mean QTcF ≥ 450 msec on screening ECG
o History of clinically manifested ischemic heart disease ≤ 6 months prior to study start
o History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by transthoracal echocardiography
o Clinically significant ECG abnormalities including one or more of the following: left bundle brunch block (LBBB), right bundle brunch block (RBBB) with left anterior hemiblock (LAHB), ST segment elevations or depressions > 1 mm or 2nd (Mobitz II) or 3rd degree AV block
o History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes
o Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
o Clinically significant resting bradycardia (< 50 beats per minute)
o Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY 922
o Obligate use of a cardiac pacemarker
• Known diagnosis of HIV, active hepatitis B and/or C (testing is not mandatory)
• Clinically symptomatic leptomeningeal or brain metastases (patients with clinically stable brain metastases may be enrolled)
• Any person being in an institution on assignment of the respective authority
• Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information
• Any serious medical condition with organ impairment
• Parallel participation in another clinical trial
• Experimental or other therapy within the last 30 days or 5 half-life's, whatever is of longer duration prior study start
• Pregnancy, breast feeding

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses


  • start of 1:1-Block address primary-sponsor
    • Universität Köln
    • Albertus-Magnus-Platz
    • 50923  Köln
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Lung Cancer Group Cologne Center for Integrated Oncology Dep.I of Internal Medicine University Hospital Collogne
    • Mr.  Prof.   Jürgen  Wolf 
    • Kerpenerstr.62
    • 50924  Köln
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Lung Cancer Group Cologne Dep.I of Internal Medicine Center for Integrated Oncology University Hospital Cologne
    • Ms.  Lucia   Nogova 
    • Kerpenerstr.62
    • 50924  Köln
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • BMBF, Projekträger DLR,
    • Ms.  Dr.  Cosima  Pfenninger 
    • Heinrich-Konen-Straße 1
    • 53227  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state


  •   Recruiting planned
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.