E7389 and Cisplatin in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

- Determine the maximum tolerated dose of E7389 and cisplatin in patients with advanced
solid tumors.

- Determine the safety and toxicity of this regimen in these patients.

- Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive E7389 IV over 5 minutes on days 1 and 8 and cisplatin IV over 30-60 minutes
on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

Cohorts of 3-6 patients receive escalating doses of E7389 and cisplatin until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which
at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients
are treated at the MTD.

Patients undergo blood collection periodically in course 1 for pharmacokinetic studies.

After completion of study treatment, patients are followed for up to 8 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant solid tumor

- Advanced disease, meeting both of the following criteria:

- Metastatic or unresectable disease

- Standard curative or palliative measures do not exist or are no longer effective

- No known active brain metastases

PATIENT CHARACTERISTICS:

- Life expectancy > 3 months

- ECOG performance status 0-2

- Bilirubin normal

- WBC ≥ 3,000/mm³

- Platelet count ≥ 100,000/mm³

- Creatinine clearance ≥ 60 mL/min

- Absolute neutrophil count ≥ 1,500/mm³

- AST and ALT ≤ 2.5 times upper limit of normal

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit study compliance

- No preexisting neuropathy ≥ grade 2

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- Recovered from prior therapy

- No prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin
C)

- No prior targeted therapy within the past 4 weeks

- No prior immunotherapy within the past 4 weeks

- No prior radiotherapy within the past 4 weeks

- No prior cumulative cisplatin dose > 300 mg/m²

- No more than 2 prior chemotherapy regimens for advanced solid tumors

- No other concurrent investigational agents

- Bisphosphonate therapy (e.g., pamidronate or zoledronate) is not considered
investigational therapy

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies