Agents targeting the epidermal growth factor receptor (EGFR) have made a major impact on the treatment of advanced NSCLC. EGFR tyrosine kinase inhibitors (TKI) erlotinib and gefitinib elicit a dramatic response in some patients with relapsed NSCLC, but resistance to that therapy is significant. Recently it was reported that irreversibly-binding EGFR-TKIs may prove highly effective in patients with EGFR activation mutations, including tumors that have become resistant to erlotinib or gefitinib.
Conditions
Interventions
Product Name: HKI-272
Pharmaceutical Form: Capsule*
INN or Proposed INN: pending
CAS Number: pending
Current Sponsor code: WAY-179272-B
Other descriptive name: HKI-272
Concentration unit: mg milligram
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathologic diagnosis of NSCLC and current stage IIIB (with pleural effusion) or IV, not curable with conventional therapy. For Arm C, diagnosis of adenocarcinoma with 1 year 2. Tumor sample available and adequate for EGFR kinase domain sequence analysis. Sequencing must be performed prior to enrollment. 3. Progression following at least twelve weeks of treatment with Tarceva or Iressa (Arms A and B only) 4. At least 1 measurable target lesion as defined by modified RECIST criteria 5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (not declining within the past 2 weeks) 6. Age >=18 years 7. Life expectancy of at least 12 weeks 8. Recovery from all clinically significant acute adverse effects of prior therapies (excluding alopecia) 9. Screening laboratory values within the following parameters: · ANC >=1.5 x 10 9/L (1,500/mm3)· Platelet count >= 75 x 10 9/L (75,000/mm3)· Hemoglobin >= 8.0 g/dL (80g/L)· Serum creatinine = =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and are clinically stable for at least 4 weeks before first dose of test article). 2. Use of Tarceva or Iressa within 14 days of treatment Day 1 (Arms A and B) or any prior therapy with EGFR/HER2 targeting treatment (Arm C). 3. More than 2 prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic disease 4. Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 3 weeks of treatment day 1 (except for Tarceva or Iressa as above) 5. Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent >400 mg/m2 6. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of >= 3. 7. Left ventricular ejection fraction less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or Echocardiogram (ECHO) 8. QTc interval > 0.47 second 9. Pregnant or breast feeding women 10. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g, Crohn’s disease, malabsorption, or Grade >= 2 diarrhea of any etiology at baseline) 11. Inability or unwillingness to swallow the HKI-272 capsules 12. Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator’s judgment, make the subject inappropriate for this study. Examples include, but are not limited to, serious active infection (i.e. requiring intravenous antibiotic or antiviral agent), uncontrolled major seizure disorder, any other active malignancy (except for NSCLC)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the objective response rate (ORR: complete plus partial responses) for HKI-272 in subjects with advanced non-small cell lung cancer.;Secondary Objective: 1. Further evaluate the safety of HKI-272 2. Assess additional efficacy parameters: clinical benefit rate (CR+PR+SD), duration of response, and progression-free survival 3. Evaluate health outcomes endpoints by administering quality of life questionnaires. 4. Evaluate the pharmacokinetics of HKI-272;Primary end point(s): Primary endpoint = objective response rate (complete plus partial responses). Objective response will be determined using modified RECIST guidelines. The primary efficacy analysis will be based on the intent-to-treat (ITT) and evaluable populations. The secondary endpoints = clinical benefit rate (CR+PR+SD), progression-free survival, duration of response, time to death, adverse event rates, pharmacokinetics, pharmacodynamics, pharmacogenomics, and health outcomes assessments (HOA). The secondary efficacy analyses will be based on the evaluable population. | — |
Countries
Hungary, Spain
Outcome results
None listed