PHASE II STUDY OF LAPATINIB IN EGFR/HER2NEU POSITIVE ADVANCED CHORDOMA - ND

• Conditions: Advanced chordoma EGFR/Her2Neu positive; MedDRA version: 9.1Level: LLTClassification code 10039492

• Registration Number: EUCTR2009-014456-29-IT
• Lead Sponsor: ISTITUTO NAZIONALE PER LA CURA TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-05
• Last Update Posted: 3 April 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Histologically proven diagnosis of chordoma (centrally review) Biomolecular or immunohistochemical evidence of lapatinib target EGFR and/or Her2/neu activation. This is mandatory. To this end, fresh material is highly recommended, preferably obtained through an incisional biopsy (to allow phospho-RTK array) or, if this is not feasible, a tru-cut biopsy (to allow direct Western Blot for EGFR and real-time PCR for TGF- and EGF ligands). However, if frozen or fresh material cannot be obtained, paraffin embedded material is also acceptable (to allow phospho-EGFR/EGFR immunohistochemistry, real-time PCR for TGF- and EGF ligands and EGFR FISH). The biomolecular and immunohistochemical assessments will be centralized to INT. Locally advanced disease (i.e. surgical resection of local disease unfeasible radically, or unaccepted by the patient, or amenable to become less demolitive, or feasible, or easier, after cytoreduction) and/or metastatic disease Measurable or evaluable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan or MRI. Evidence of progressive disease in the previous 6 months Estern Cooperative Oncology Group (ECOG) Performance Status 0-2 Adequate bone marrow function, defined as the following: ANC >1.5 x 109/L, platelets >100 x 109/L, Hb >9 g/dL. Blood transfusions are allowed to reach the baseline requested Hb level Adequate organ function, defined as the following: total bilirubin within normal institutional limits (but in case of Gilbert s syndrome), AST (SGOT) and ALT (SGPT) <2.5 x UNL, creatinine <1.5 x ULN. within normal institutional limits or creatinine clearance  60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal Cardiac ejection fraction ≥50% as measured by echocardiogram. Age > 18 yrs Written, voluntary informed consent Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse Previous treatment with any other investigational or not investigational agents and or radiation therapy within 28 days of first day of study drug dosing. or patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier Major surgery within 2 weeks prior to study entry Previous radiotherapy to 25 % of the bone marrow Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors (see Appendix 1). Steroids are allowed when strictly necessary according to clinical investigator evaluation Concomitant other investigational agents or concurrent anticancer therapy. In addition, all herbal (alternative) medicines are excluded Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e., history of uncontrolled or symptomatic angina, history of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation, myocardial infarction < 6 months from study entry, uncontrolled or symptomatic congestive heart failure, ejection fraction below the institutional normal limit) Known brain metastasis Known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis with exception of patients with Gilbert`s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) Known diagnosis of human immunodeficiency virus (HIV) infection History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lapatinib Expected non-compliance to medical regimens

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Overall tumor Response Rate, according to Choi criteria extended even to MRI.;Secondary Objective: 1. RECIST response rate 2. PET response rate 3. Overall Survival 4. Progression Free Survival 5. Clinical Benefit 6. Post-treatment EGFR and/or Er2/Neu status assessment;Primary end point(s): Overall tumor Response Rate, according to Choi criteria extended even to MRI.