• Maximum tolerated dose [ Designated as safety issue: Yes ]
• Recommended phase II dose [ Designated as safety issue: Yes ]
• Safety, tolerability, toxicity profile, and dose-limiting toxicity [ Designated as safety issue: Yes ]
• Pharmacokinetic profile [ Designated as safety issue: No ]

• Maximum tolerated dose
• Recommended phase II dose
• Safety, tolerability, toxicity profile, and dose limiting toxicity of E7389
• Pharmacokinetic profile of E7389 and gemcitabine hydrochloride

• Preliminary clinical antitumor activity [ Designated as safety issue: No ]
• Objective response rate in patients with measurable disease, as measured by RECIST criteria [ Designated as safety issue: No ]
• Duration of response and time to disease progression in patients with measurable disease [ Designated as safety issue: No ]

• Objective response rate as measured by RECIST criteria, duration of response, and time to disease progression in patients with measurable disease
• Preliminary clinical antitumor activity of E7389

RATIONALE: Drugs used in chemotherapy, such as E7389 and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of E7389 and gemcitabine in treating patients with metastatic or unresectable solid tumors.

OBJECTIVES:

• Determine the recommended phase II dose of E7389 and gemcitabine hydrochloride in patients with metastatic or unresectable solid tumors.
• Determine the safety, tolerability, and toxicity profile of this regimen in these patients.
• Assess the antitumor activity of this regimen in patients with measurable disease.
• Determine the pharmacokinetic profile of this regimen to assess possible interactions between the two drugs.

OUTLINE: This is a dose-escalation study.

Patients receive E7389 IV and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 OR on days 1 and 8*. Treatment repeats every 28 or 21 days* in the absence of disease progression or unacceptable toxicity.

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

NOTE: *If the MTD is determined at the first dose level of the 28-day schedule, subsequent patients are treated on a 21-day schedule and receive treatment on days 1 and 8.

After completion of study treatment, patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

• Drug: eribulin mesylate
• Drug: gemcitabine hydrochloride

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

  • Metastatic or unresectable disease
  • Standard curative antineoplastic drug therapy does not exist or is no longer effective
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelets ≥ 100,000/mm³
• Bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions to agents of similar chemical or biological composition to E7389 or gemcitabine hydrochloride

• 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/social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy

• At least 4 weeks since prior radiation therapy

  • No more than 40% of bone marrow radiated
  • Must have measurable disease outside the radiation field or show disease progression after prior radiation therapy
• At least 4 weeks since prior major surgery
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• No more than 2 prior chemotherapy regimens for advanced or metastatic incurable solid tumors

  • Prior neoadjuvant chemotherapy is not counted towards the 2 prior chemotherapy regimens
• At least 4 weeks since prior biologic therapy or hormonal therapy
• No prior gemcitabine hydrochloride
• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent inhibitors or inducers of CYP3A4

  • Concurrent use of CYP3A4 substrates allowed
• No concurrent prophylactic colony-stimulating factors
• No other concurrent investigational agents
• No other concurrent anticancer therapy (e.g., hormonal therapy, biologic therapy, or targeted therapies)