This non-randomized, open-label, outpatient clinical trial is designed to assess the safety and efficacy of daily orally administered EKB-569 in subjects with advanced non-small cell lung cancer. Patients must have been previously treated with a platinum- and docetaxel-based therapy either given concurrently or as separate regimens.

The primary objective of the study is to assess the clinical activity of EKB-569 administered orally as a second-line or later stage treatment in subjects with advanced non-small cell lung cancer. Secondary objectives include:

• To further evaluate the safety of EKB-569
• To explore additional clinical activity parameters
• To explore subject survival
• To evaluate the pharmacokinetics of EKB-569
• To assess subject reported outcomes

EKB-569 will be administered orally as a single-agent. Eligible subjects will take EKB-569 daily as long as they do not have progressive disease and are tolerating treatment.

Condition	Treatment or Intervention	Phase
Non-Small-Cell Lung Carcinoma Carcinoma, Non-Small Cell Lung	Drug: EKB-569	Phase II

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Signed and dated, institutional review board (IRB) or independent ethics committee (IEC)-approved informed consent form before any protocol-specific screening procedures.
• Histologic and/or cytologic diagnosis of locally-advanced or metastatic non-small cell lung cancer in subjects who are not curable by conventional therapy.
• Progression (or unacceptable toxicity) after platinum- (e.g., carboplatin or cisplatin) and docetaxel-based chemotherapy, either given concurrently (1 regimen) or as separate treatments (adjuvant or neo-adjuvant chemotherapy does not count as prior chemotherapy treatment).
• Measurable disease defined by the presence of at least 1 measurable lesion ≥ 20 mm by conventional techniques, or ≥ 10 mm by spiral computed tomography (CT) scan, or ≥ 2 x slice thickness.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (not declining within the past 2 weeks).
• Age 18 years or older.
• Recovery from all acute adverse effects of prior therapies (excluding alopecia).
• Adequate renal, hepatic and bone marrow function
• For women of childbearing potential, a negative serum pregnancy test at screening.
• Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use medically acceptable methods of birth control (eg, cervical cap, diaphragm with spermicide, condom with spermicide, or intrauterine device) for the duration of the active phase of the study, and for 30 days after the last dose of test article.

Exclusion Criteria:

• Chemotherapy, radiotherapy, anticancer immunotherapy, or investigational agents within 4 weeks of treatment day 1 (6 weeks if the previous regimen included mitomycin or nitrosoureas).
• Prior radiotherapy to >25% of bone marrow.
• Prior epidermal growth factor receptor-targeting therapy.
• Use of immunosuppressive agents, including systemic corticosteroids, within 4 weeks of screening (corticosteroids are permitted in physiological replacement doses and as symptomatic episodic treatment of nausea).
• Central nervous system (CNS) metastases.
• Major surgery within 2 weeks of screening.
• Concurrent serious infection (ie requiring an intravenous antibiotic or antiviral agent).
• Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn’s disease, ulcerative colitis, malabsorption syndrome, Grade ≥ 2 diarrhea of any etiology at baseline).
• Inability to swallow the EKB-569 capsule.
• Breastfeeding of infants during the study or within 30 days after the last dose of test article.
• Evidence of significant skin disorder with symptomatic rash.

California
      John Wayne Cancer Institute, Santa Monica,  California,  90404,  United States
Colorado
      University of Colorado, Denver,  Colorado,  80262,  United States
Florida
      Jacksonville Regional Cancer Center, Jacksonville,  Florida,  32207,  United States
      Ocala Oncology, Ocala,  Florida,  34474,  United States
      Florida Cancer Institute Clinical Research, New Port Richey,  Florida,  34452,  United States
Illinois
      Midwestern Regional Medical Center, Zion,  Illinois,  60099,  United States
Kansas
      University of Kansas, Kansas City,  Kansas,  United States
Louisiana
      Oschner Clinic Foundation, New Orleans,  Louisiana,  70121,  United States
Maryland
      Greater Baltimore Medical Center, Baltimore,  Maryland,  21204,  United States
Michigan
      Henry Ford Health Center/Josephine Ford Cancer Center, Detroit,  Michigan,  48202,  United States
Mississippi
      North Mississipi Hematology and Oncology Associates, Ltd., Tupelo,  Mississippi,  38801,  United States
South Carolina
      WJB Dorn VA Medical Center, Columbia,  South Carolina,  29209,  United States
Washington
      Swedish Cancer Institute/PSOC, Seattle,  Washington,  98104,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
      Medical Consultants, LTD, Milwaukee,  Wisconsin,  53215,  United States

Study ID Numbers:  3095A1-201-WW
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  August 21, 2003
ClinicalTrials.gov Identifier:  NCT00067548
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08