Phase I Clinical Study of E7389
Condition: Cancer
Intervention: E7389
Intervention description: E7389 will be administered intravenously on Days 1 and 8 of a 21 day cycle. The initial dose level will be 0.7 mg/m2, with planned dose levels of 1.0, 1.4, 2.0 mg/m2.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 20 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: Cancer; Tumors; Phase I; E7389

Summary:

      The primary objective of this study is to determine the dose limiting toxicity and maximum
      tolerated dose of E7389 in patients with solid tumors. The secondary objectives are to
      investigate the pharmacokinetics, safety, estimated recommended dose, and anti-tumor effects
      (in evaluable cases) of E7389 in patients with solid tumors.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with histologically or cytologically confirmed solid tumors.

          2. Patients who have progressed on or following standard therapy and with no other
             treatment options.

          3. Patients aged 20-74 when they give informed consent.

          4. Patients having a performance status (PS) of Eastern Cooperative Oncology Group (ECOG)
             0 or 1.

          5. Patients who can stay at the hospital from the start of the study drug treatment to 2
             weeks of the first cycle.

          6. Patients having adequate function of major organs (bone marrow, liver, kidney and
             lungs):

        (1) Neutrophil count 1,500/mm3 (2) Platelet count 100,000/mm3 (3) Hemoglobin 9.0 g/dL (4)
        Aspartate aminotransferase [AST] 2.5 times the upper limits of normal (ULN) in institute,
        unless related to liver involvement by tumor, in which case 5.0 times ULN (5) Alanine
        aminotransferase [ALT] 2.5 times ULN in institute, unless related to liver involvement by
        tumor, in which case 5.0 times ULN (6) Total bilirubin 1.5 times ULN in institute (7) Serum
        creatinine 1.5 times ULN in institute (8) Pulse oximeter oxygen saturation 90%

        7. Patients with no adverse drug reactions (excluding alopecia, etc.) that were caused by
        the prior therapy or could influence the safety evaluation of the study drug.

        The withdrawal periods required from the completion of the prior therapy to the start of
        the study drug therapy are as follows:

          1. Chemotherapy (excluding oral 5-FU and molecular target drugs), surgical therapy, other
             study drugs: 4 weeks

          2. Nitrosourea agents, mitomycin C: 6 weeks

          3. Radiotherapy, endocrinotherapy, immunotherapy, oral 5-FU, molecular target drugs,
             blood transfusion, blood products, G-CSF and other hematopoietic factors: 2 weeks

        8. Patients who give written informed consent.

        9. Patients with an expected survival of longer than 3 months from the start of the study
        drug therapy.

        Exclusion criteria:

          1. Patients with systemic infection with a fever (38°C).

          2. Patients with a large amount of pleural effusion, ascites and pericardial fluid
             requiring drainage.

          3. Patients with brain metastasis with clinical symptoms.

          4. Patients with serious complications: (1) Patients with uncontrollable cardiac disease
             such as ischemic heart disease and arrhythmia at a level of severity that needs to be
             treated (excluding left ventricular hypertrophy, mild left ventricular volume overload
             and mild right leg block that accompany hypertension) (2) Patients with myocardial
             infarction within 6 months prior to study entry (3) Patients with a complication of
             hepatic cirrhosis (4) Patients with interstitial pneumonia and pulmonary fibrosis (5)
             Patients with a bleeding tendency

          5. Women who are pregnant or breastfeeding, or premenopausal women of childbearing
             potential.

             Post-menopausal women must be amenorrheic for at least 12 months to be considered of
             non-childbearing potential. Premenopausal women of childbearing potential with either
             a positive pregnancy test at screening or no pregnancy test, or have not agreed to use
             adequate measures of contraception.

          6. Fertile men who are not willing to use contraception or fertile men with a female
             partner who is not willing to use contraception.

          7. Patients who have tested positive for human immunodeficiency virus (HIV), hepatitis C
             virus (HCV) antibody, or hepatitis B virus surface antigen (HBsAg).

          8. Patients who need continuous systemic steroid therapy during the study period.

          9. Patients who need continuous use of phenytoin, carbamazepine, rifampicin and/or
             barbiturate which induces cytochrome P450 (CYP3A4), a drug-metabolizing enzyme, during
             the study period.

         10. Patients who have received extensive radiation therapy (30% or more of bone marrow).

         11. Patients who refused to receive a supportive therapy of blood transfusion by
             suppressing bone marrow.

         12. Patients who are participating in other clinical studies.

         13. Patients whom the investigator or subinvestigator has judged inappropriate for this
             study.