A Phase 2 Study of HKI-272 in Subjects with Advanced Non-Small Cell Lung Cancer

• Conditions: 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.

• Registration Number: EUCTR2005-003097-19-HU
• Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-21
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 188

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 =10 pack-years smoking history and current non-smoker for =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 = <=1.5 x upper limit of normal (ULN)· Total bilirubin = <=1.5 x ULN· AST and ALT = <= 2.5 x ULN (= <5 x ULN if liver metastases are present)
10.For women of child bearing potential, a negative serum pregnancy test result before study entry. A woman of child bearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
11.Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use medically acceptable methods of birth control for the duration of the study and for 28 days after the last dose of test article.
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

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 3 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)

Study & Design

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