Phase II Study Of E7389, Halichondrin B Analogue, In Patients With Advanced Non-Small Cell Lung Cancer, NSCLC, Who Progressed During Or After Platinum-Based Doublet Chemotherapy
Condition: Non-Small-Cell Lung Carcinoma
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: E7389 28 Day Cycle; E7389 21 Day Cycle
Intervention description: E7389 1.4 mg/m^2 IV bolus on Days 1, 8, and 15 of a 28 day cycle.; E7389 1.4 mg/m^2 IV bolus on Days 1 and 8 of a 21 day cycle.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 106.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study of E7389 in patients with recurrent and/or metastatic Non-Small-Cell Lung
      Cancer (NSCLC) who progressed during or after treatment with a platinum agent and another
      chemotherapy.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Patients must have a histologically or cytologically confirmed diagnosis of non-small
             cell lung cancer with at least one site of measurable disease by the RECIST criteria.

          -  Patients must have failed prior platinum-containing doublet chemotherapy. Patients who
             have received single agent chemotherapy with or without a subsequent taxane containing
             regimen may be enrolled after discussion with Sponsor.

          -  Patients must be ≥ 18 years of age.

          -  Patients must have a performance score of 0 or 1 using the ECOG performance scale.

          -  Patients must have a life expectancy of ≥ 3 months.

          -  Patients must have adequate renal function as evidenced by a serum creatinine ≤ 2.0
             mg/dL or a calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault
             formula.

          -  Patients must have adequate hepatic function as evidenced by bilirubin ≤1.5 mg/dL and
             alkaline phosphatase, AST and ALT ≤ 3 times upper limit of normal, unless there is
             evidence of liver metastases, in which case the alkaline phosphatase, AST and ALT must
             be ≤ 5 times upper limit of normal.

          -  Patients must have adequate bone marrow function as evidenced by absolute neutrophil
             counts (ANC) ≥ 1.5 X 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin < 10.0 g/dL would be
             acceptable if it can be corrected by growth factor or transfusion), and platelet count
             ≥ 100 X 10^9/L.

          -  Patients must be willing and able to comply with the protocol guidelines for the
             duration of the study.

          -  Patients must be willing and able to complete the Lung Cancer Symptom Scale (LCSS)
             instrument.

          -  The biopsy specimen (paraffin block or at least 10 unstained slides) must be available
             from either the initial diagnosis or any subsequent diagnostic or surgical procedure
             of patients participating in the pharmacogenomics sub-study only. However, no
             additional biopsies are obligatory for participation in this study except those
             required for confirmation of the diagnosis.

          -  Patients must give written informed consent prior to any study-specific screening
             procedures with the understanding that the patient may withdraw consent at any time
             without prejudice.

        EXCLUSION CRITERIA:

          -  Patients with pre-existing peripheral neuropathy > Grade 2

          -  Patients who require therapeutic doses of warfarin

          -  Patients who have not recovered from any chemotherapy, radiation or other therapy
             related toxicity deemed to be clinically significant at study entry

          -  Patients with active symptomatic brain metastases. Patients with central nervous
             system (CNS) metastases are considered eligible if they have had adequately treated
             brain metastases, i.e. have completed treatment (tapered off steroids) at least four
             weeks before starting treatment with E7389. Patients who have no evidence that the
             metastases are symptomatic or actively growing (no evidence of midline shift on CT
             scan or MRI) may be enrolled without initiation of local therapy for the CNS
             metastases. In this case, a repeat scan must be performed within four weeks of the
             original scan to ensure that disease progression is not occurring. It is not the
             intention of this study to treat patients with active brain metastases.

          -  Patients who have a positive history for HIV, active hepatitis B or active hepatitis
             C.

          -  Patients with other significant medical, or psychiatric disorders that, in the opinion
             of the investigator, will exclude the patient from the study for compliance or safety
             reasons

          -  Patients who have received investigational drugs, including immunotherapy, gene
             therapy, hormone therapy (except megestrol acetate for appetite stimulation), or other
             biological therapy; conventional chemotherapy or radiation therapy (except for
             palliation, defined as less than 10% of the bone marrow reserve and less than 20 Gy),
             within three weeks of E7839 enrollment

          -  Patients who have received non-cytotoxics (eg, gefitinib, erlotinib) within one week
             of E7389 enrollment

          -  Patients who have not recovered from major surgery within three weeks of E7389
             enrollment

          -  Patients with severe/uncontrolled intercurrent illness/infection

          -  Patients with significant cardiovascular impairment (history of congestive heart
             failure>NYHA grade II, unstable angina or myocardial infarction within the past six
             months, or serious cardiac arrhythmia)

          -  Patients with organ allografts

          -  Patients with hypersensitivity to halichondrin B and/or halichondrin B-related
             compounds

          -  Patients who participated in a prior E7389 clinical trial

          -  Patients with second malignancy within the past 5 years, except for carcinoma in situ
             of the cervix or basal cell carcinoma of the skin

          -  Women who are pregnant or breast-feeding; woman of childbearing potential with a
             positive pregnancy test at screening or no pregnancy test. Women of childbearing
             potential unless (1) surgically sterile or (2) using adequate measures of
             contraception in the opinion of the Investigator. Perimenopausal women must be
             amenorrheic for at least 12 months or using adequate contraception to be considered of
             non-childbearing potential.

          -  Fertile men who are not willing to use contraception or fertile men with a female
             partner who is not willing to use contraception