This phase I trial is studying the side effects and best dose of eribulin mesylate and gemcitabine hydrochloride in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as eribulin mesylate and gemcitabine hydrochloride, 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.
OBJECTIVES: I. Determine the recommended phase II dose (RPTD) of E7389 (eribulin mesylate) when given in combination with gemcitabine (gemcitabine hydrochloride) in patients with advanced cancer. II. Determine the safety, tolerability, and toxicity profile of E7389 and gemcitabine given in combination. III. Assess the antitumor activity of E7389 in combination with gemcitabine in patients with measurable disease. IV. Determine the pharmacokinetic profile of E7389 and gemcitabine to assess for any possible interactions between the two agents. OUTLINE: This is a multicenter, dose-escalation study. Patients receive eribulin mesylate intravenously (IV) and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 OR on days 1 and 8. Courses repeat every 28 or 21 days\* in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of eribulin mesylate 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 (DLT). NOTE: \*If DLT is observed at the first dose level of the 28-day schedule, subsequent patients are treated on days 1 and 8 of the 21-day schedule; patients enrolled in the expansion cohort (patients with ovarian or endometrial cancer or chemotherapy-naive or minimally pre-treated cancer) receive treatment according to the 21-day schedule. After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Given IV
Given IV
Ottawa Hospital-Civic Campus
Ottawa, Ontario, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
Maximum tolerated dose of eribulin mesylate administered with gemcitabine hydrochloride in advanced/metastatic solid tumors
The Common Terminology Criteria for Adverse Events (CTCAE version 3 will be used to grade toxicity.
Time frame: Course 1
Recommended phase II dose of eribulin mesylate in combination with gemcitabine hydrochloride
Defined as one dose level below the dose at which 2 or more patients experience a DLT. If =\< 1 DLT is observed at dose level 5, then this will be the RPTD.
Time frame: Course 1
Safety, tolerability, toxicity profile, and dose-limiting toxicity of eribulin mesylate
Graded using the CTCAE version 3.
Time frame: From the time of their first treatment with eribulin mesylate
Pharmacokinetic profiles of eribulin mesylate and gemcitabine hydrochloride
Plasma samples for the determination of eribulin mesylate plasma concentration will be analyzed in conjunction with Eisai Pharmaceuticals. Plasma samples for the determination of gemcitabine plasma concentration will be analyzed through methods developed at the Princess Margaret Hospital.
Time frame: Days 1, 2, 3, 5, and 8 of course 1
Preliminary clinical antitumor activity of eribulin mesylate
Assessed using radiologic images (CT scans). Measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time frame: Baseline, every 2 courses, and 4 weeks post-treatment
Objective response rate in patients with measurable disease
Measured by RECIST criteria. All tests will be two-sided and a p-value of 0.05 or less will be considered statistically significant. Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. 95% confidence intervals will be provided for estimates of interest where possible.
Time frame: Baseline, every 2 courses, and 4 weeks post-treatment
Duration of response in patients with measurable disease
Estimated using the Kaplan-Meier method.
Time frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
Time to disease progression in patients with measurable disease
Estimated using the Kaplan-Meier method.
Time frame: From start of treatment until the criteria for progression are met
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