Eribulin Mesylate and Gemcitabine Hydrochloride in Treating Patients With Metastatic Solid Tumors or Solid Tumors That Cannot be Removed by Surgery
|Adult Solid Neoplasm Recurrent Ovarian Carcinoma Recurrent Uterine Corpus Carcinoma Stage III Ovarian Cancer Stage III Uterine Corpus Cancer Stage IV Ovarian Cancer Stage IV Uterine Corpus Cancer||Drug: Eribulin Mesylate Drug: Gemcitabine Hydrochloride||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Halichondrin B Analog E7389 in Combination With Gemcitabine in Patients With Refractory or Advanced Solid Tumors|
- Maximum tolerated dose of eribulin mesylate administered with gemcitabine hydrochloride in advanced/metastatic solid tumors [ Time Frame: Course 1 ]The Common Terminology Criteria for Adverse Events (CTCAE version 3 will be used to grade toxicity.
- Pharmacokinetic profiles of eribulin mesylate and gemcitabine hydrochloride [ Time Frame: Days 1, 2, 3, 5, and 8 of course 1 ]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.
- Recommended phase II dose of eribulin mesylate in combination with gemcitabine hydrochloride [ Time Frame: Course 1 ]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.
- Safety, tolerability, toxicity profile, and dose-limiting toxicity of eribulin mesylate [ Time Frame: From the time of their first treatment with eribulin mesylate ]Graded using the CTCAE version 3.
- Duration of response in patients with measurable disease [ 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 ]Estimated using the Kaplan-Meier method.
- Objective response rate in patients with measurable disease [ Time Frame: Baseline, every 2 courses, and 4 weeks post-treatment ]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.
- Preliminary clinical antitumor activity of eribulin mesylate [ Time Frame: Baseline, every 2 courses, and 4 weeks post-treatment ]Assessed using radiologic images (CT scans). Measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Time to disease progression in patients with measurable disease [ Time Frame: From start of treatment until the criteria for progression are met ]Estimated using the Kaplan-Meier method.
|Actual Study Start Date:||November 14, 2006|
|Primary Completion Date:||October 24, 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (combination chemotherapy)
Patients receive eribulin mesylate 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.
Drug: Eribulin Mesylate
Given IVDrug: Gemcitabine Hydrochloride
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00410553
|Ottawa Hospital-Civic Campus|
|Ottawa, Ontario, Canada, K1Y 4E9|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Rakesh Goel||University Health Network-Princess Margaret Hospital|