Study of E7389 in Patients With Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: E7389
Intervention description: E7389 Dose-escalation starting at 0.25 mg/m^2 intravenous on Days 1, 8, and 15 of a 28 day cycle.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Tumors; Advanced Solid Tumors; Stage IV Tumors; Solid Tumors; Recurrent Solid Tumors

Summary:

      To determine the maximum tolerated dose of E7389 in patients with advanced solid tumors that
      have progressed following standard therapy or for which no standard therapy exists.
    

Eligibility criteria:

        Inclusion Criteria

          -  Patients must have a histologically or cytologically confirmed and measurable advanced
             solid tumor that has progressed following standard therapy or for which no standard
             therapy exists (including surgery or radiation therapy)

          -  Patients may have received prior chemotherapy

          -  Patients must be aged > 18 years

          -  Patients must have a Karnofsky Performance Status of > 70%

          -  Patients must have a life expectancy of > 3 months

          -  Patients must have adequate renal function as evidenced by serum creatinine <1.5mg/dL
             or creatinine clearance >= 45mL/minute

          -  Patients must have adequate bone marrow function as evidenced by absolute neutrophil
             count > 1,500/µL and platelets > 100,000/µL

          -  Patients must have adequate liver function as evidenced by bilirubin < 1.5mg/dL and
             alanine transaminase (ALAT) and aspartate transaminase (ASAT) <= 2 times the upper
             limits of normal (ULN)unless related to liver involvement by tumor, in which case <=
             5.0 times ULN

          -  Patients must be willing and able to comply with the study protocol for the duration
             of the study

          -  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 who have received chemotherapy within three weeks (six weeks if nitrosoureas
             were received) of E7389 treatment start

          -  Patients who have not recovered from any chemotherapy related or other therapy related
             toxicity at study entry

          -  Patients who require active anti-coagulant therapy

          -  Women who are pregnant or breastfeeding. Women of childbearing potential with either 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 (postmenopausal women must be
             amenorrheic for at least 12 months 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

          -  Patients who have not successfully completed local therapy for previously treated
             central nervous system (CNS) metastases and who have not been discontinued from
             corticosteroids for at least four weeks before starting treatment with E7389. Patients
             with asymptomatic brain metastases who have 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.

          -  Patients who have tested positive for HIV

          -  Patients with severe uncontrolled intercurrent illness/infection (excluding
             malignancies)

          -  Patients with uncontrolled cardiovascular illness defined as unstable angina,
             myocardial infarction within 6 months prior to study entry, symptomatic congestive
             heart failure (CHF) (NYHA II or higher) clinical evidence of CHF, or clinical evidence
             of serious cardiac arrhythmia

          -  Patients with organ allografts

          -  Patients who have received investigational drugs, including immunotherapy, gene
             therapy, hormone therapy, or other biologic therapy; anti-neoplastic therapy; or
             radiation therapy (other than required for palliation) within three weeks of E7389
             treatment start

          -  Patients who have had major surgery within four weeks of E7389 treatment start without
             a full recovery

          -  Patients with a hypersensitivity to Halichondrin B and/or Halichondrin B-like
             compounds

          -  Patients with other significant disease that, in the Investigator's opinion, would
             exclude the patient from the study