Trastuzumab and AUY922 in HER2-aberrant NSCLC

Phase 1

• Conditions: Advanced non-smallcell lung cancer with HER2 - overexpression or - amplification or - mutation; MedDRA version: 17.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005655-13-DE
• Lead Sponsor: niversity of Cologne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-05-10
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 29

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 < 1.5 x ULN
o Creatinine clearence (CrCl) = 60ml/min calculated by either MDRD-formel or
by 24 hours urine collection
o Total calcium (corrected for serum albumin) within normal limits or
correctable with supplements.
o Magnesium within lower 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
- effective method of contraception (Pearl-Index not greater than 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 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

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. < 2mg/day) are permitted
• Patients with concurrent severe and/or uncontrolled medical conditions (e.g.
uncontrolled diabetes mellitus, active untreated or uncontrolled infection,
chronic obstructive or chronic restrictive pulmonary disease including
dyspnea at rest from any cause or requiring supplementary oxygen therapy)
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 QTc = 450 msec on screening ECG
o History of clinically manifest ischemic heart disease = 6 months prior
to start of the study
o History of heart failure or left ventricular (LV) dysfunction (LVEF =
45%) by transthoracic 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 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified