AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy
Condition: Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence
Intervention: saracatinib
Intervention description: Given PO
Intervention MeSH terms: Saracatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well saracatinib works in treating patients with
      recurrent, stage IIIB or stage IV non-small cell lung cancer previously treated with
      combination chemotherapy that included cisplatin or carboplatin. Saracatinib may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recurrent/metastatic/locally advanced unresectable, histologically or cytologically
             confirmed NSCLC

          -  Measurable disease defined (RECIST) as at least 1 lesion measured in at least 1
             dimension (longest diameter) as >20mm with conventional techniques or >10mm with
             spiral CT scan

          -  Previously treated with firstline platinum-based systemic chemotherapy for advanced
             disease AND had at least disease stabilization as best response to firstline therapy

               -  <=1 line of prior therapy

               -  Not have had prior treatment with EGFR Tyrosine kinase inhibitor

               -  Completed chemotherapy/surgery/radiotherapy 4 weeks before study entry and must
                  have recovered from toxic effects of prior therapy

               -  Had >40% of their bone marrow radiated and must have either measurable disease
                  outside field/documented progression post radiation therapy

          -  Life expectancy >3 months

          -  ECOG performance status =<2 OR Karnofsky >=60%

          -  Leukocytes >=3x10^9/L

          -  Absolute neutrophil count >=1.5x10^9/L

          -  Platelet count >=10x10^9/L

          -  Hemoglobin >9g/dL (may be transfused to meet this)

          -  Total bilirubin =<1.5 times institutional ULN (IULN)

          -  AST/ALT =<2.5xIULN (=<5 times ULN in the presence of liver metastases)

          -  Creatinine =<1.5xIULN OR creatinine clearance >=50 mL/min/1.73m^2

          -  Urine protein creatinine ratio =<1.0 OR urine protein >1.0, 24 hour urine for protein
             should be <1000mg

          -  Women of childbearing potential/men must use adequate contraception (hormonal/barrier
             method of birth control; abstinence) prior to study entry, for duration of study
             participation, and for 8 weeks following cessation of study therapy

          -  Ability to understand/willingness to sign written informed consent

        Exclusion Criteria:

          -  Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas/mitomycin C) prior
             to study entry/not recovered from AEs due to agents administered > than 4 weeks
             earlier

          -  No CYP3A4-active agents permitted during protocol treatment. Patients requiring
             treatment with these agents are not eligible; prohibited drugs should be discontinued
             7 days before first dose of AZD0530 and for 7 days after discontinuation of AZD0530

          -  Cannot receive other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical/biologic
             composition to AZD0530

          -  QTc prolongation (i.e.QTc interval >=460 msec)/other significant ECG abnormalities

          -  Poorly controlled hypertension (i.e.systolic BP of 140 mmHg or higher, diastolic BP of
             90mm Hg or higher)

          -  Any condition impairing ability to swallow AZD0530 tablets

          -  Treated brain metastases which are clinically and radiologically stable are permitted;
             patients requiring steroids/with neurological symptoms should be excluded because of
             poor prognosis/often develop progressive neurologic dysfunction

          -  Intercurrent cardiac dysfunction including but not limited to symptomatic congestive
             heart failure, unstable angina pectoris, or cardiac arrhythmia are excluded as are
             those with ischemic heart disease history including myocardial infarction

          -  Uncontrolled intercurrent illness including but not limited to ongoing/active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women excluded because AZD0530 has potential teratogenic/abortifacient
             effects; because unknown but potential risks for AEs in nursing infants secondary to
             treatment of mother with AZD0530, breastfeeding should be discontinued if mother is
             treated with AZD0530

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because
             potential for PK interactions with AZD0530; these patients have increased risk of
             lethal infections when treated with marrow-suppressive therapy; appropriate studies
             will be undertaken in patients receiving combination antiretroviral therapy when
             indicated