Advanced non-small cell lung cancer with HER2 - overexpression or - amplification or - mutation MedDRA version: 17.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Herceptin
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Other descriptive name: rhuMAb
Concentration unit:
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Stage IV NSCLC patients after failure of at least one standard therapy with HER2 protein overexpression (HER2 score 3+) 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 the following laboratory requirements conducted at least 14 days prior to treatment: o Hemoglobin = 8.5 g/dL o Absolute neutrophil count (ANC) = 1000 / µl o Platelet count = 80,000/µL o Total bilirubin = 2 x ULN o ALT, AST and alkaline phosphatase (AP) = 2.5 x ULN o PT-INR/PTT =65 years) yes F.1.3.1 Number of subjects for this age range 8
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 sodium warfarin (coumadin). Low doses of coumadin (e.g. 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 or history of unstable hypertension) 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 AUY922 o Obligate use of a cardiac pacemarker o Angina pectoris requiring a medicinal producto Evidence of transmural infarction on ECG o Clinically significant valvular disease • 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 (with exception of trastuzumab, if patient is recruited directly for combination treatment) • Pregnancy, breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of combined trastuzumab and AUY922 in HER2 - overexpressed or - amplified or - mutated NSCLC;Secondary Objective: • To evaluate the response rate in patients treated with trastuzumab monotherapy • To evaluate the tolerability of trastuzumab and AUY922 in combination (endpoints: assessment of adverse events (AEs) according to CTC-AE V4.0) • To evaluate the clinical efficacy of trastuzumab monotherapy and the combination descriptively (endpoints: progression-free survival (PFS), overall survival (OS)) • To assess correlation of outcome parameters with the type of genetic aberration of HER2 (amplification, mutation) descriptively • To assess pharmacokinetics of AUY922 and trastuzumab • To establish a pharmacokinetic / pharmacodynamic model with regard to response rate and adverse events;Primary end point(s): • Response rate • Assessment of adverse events (AEs) according to CTC-AE V4.0 • progression-free survival (PFS), overall survival (OS);Timepoint(s) of evaluation of this end point: CT every 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Assessment of adverse events (AEs) according to CTC-AE V4.0 • progression-free survival (PFS), overall survival (OS) • To assess correlation of outcome parameters with the type of genetic aberration of HER2 (amplification, mutation) descriptively • To assess pharmacokinetics of AUY922 and trastuzumab • To establish a pharmacokinetic / pharmacodynamic model with regard to response rate and adverse events;Timepoint(s) of evaluation of this end point: • Every visit during the trial • CT every 6 weeks, contact by phone every 6 months (after study discontinuation) • Assessment of genetic type (once Screening phase) and CT every 6 mont • PK D1, D2, D5, D8, D22, D36, after then 2 weekly • To establish a pharmacokinetic / pharmacodynamic model with regard to response rate and adverse events | — |
Countries
Germany
Contacts
Public ContactLung Cancer Group Cologne
University Hospital of Cologne
Outcome results
None listed