This phase Ib trials studies the side effects and best dose of eribulin mesylate when given together with radiation therapy in treating patients with retroperitoneal liposarcoma that can be removed by surgery. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells.
PRIMARY OBJECTIVE: I. To determine the recommended phase 2 dose (RP2D) of radiation and eribulin mesylate (eribulin) when used in combination for the preoperative treatment of retroperitoneal liposarcoma. SECONDARY OBJECTIVES: I. To assess the feasibility of a preoperative chemoradiation protocol for retroperitoneal liposarcoma. II. To assess the surgical outcomes of retroperitoneal liposarcoma resections after preoperative chemoradiation. III. To assess preliminary anti-tumor activity of eribulin in combination with radiation in subjects with retroperitoneal liposarcoma. OUTLINE: This is a dose-escalation study of eribulin mesylate. Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8 and undergo intensity-modulated radiation therapy once daily (QD) 5 days a week beginning on day 8 of cycle 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo surgery within 3-10 weeks after radiation therapy. After completion of study treatment, patients will be followed up at 2 weeks, 9 weeks, and then every 6 months for 10 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Given IV
Undergo IMRT
Correlative studies
Ancillary studies
Ancillary studies
Undergo surgery
OHSU Knight Cancer Institute
Portland, Oregon, United States
Incidence of dose limiting toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03
All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Serious adverse events (SAE) specific incidence and exact 95% confidence interval will be provided where appropriate.
Time frame: Up to 42 days
Rate of enrollment
Time frame: Up to 18 months
Rate of early surgical resection
The proportion of subjects, along with exact two-sided 95% confidence intervals, undergoing surgical resection before the completion of all planned chemotherapy and radiation will be reported for the study.
Time frame: 3 weeks after radiation therapy
Rate of surgical resection
The proportion of subjects, along with exact two-sided 95% confidence intervals, undergoing surgical resection later than planned for any reason will be reported for the study.
Time frame: After 10 weeks of radiation, until study completion (up to 4 years)
Change in subject-reported quality of life assessed by Patient-Reported Outcomes Measurement Information System (PROMIS)
Will apply a mixed effects model to analyze changes in PROMIS symptom measurements at four time points: baseline, C2D8, prior to surgery and 9 weeks postoperative (post-op).
Time frame: Baseline up to 9 weeks after surgery
Rate of R0 resection defined as the proportion of surgical specimens with microscopically negative margins
The rate of R0 resection, along with exact two-sided 95% confidence intervals, will be reported for the study.
Time frame: Up to 10 years
Rate of serious post-operative complications
This rate, along with exact two-sided 95% confidence intervals, will be reported for the study.
Time frame: Up to 9 weeks following surgery
Pathologic response defined as the percentage of tumor with treatment change, including necrosis, fat maturation and hyalinization
Descriptive statistics including mean, median, standard deviation, and 95% confidence interval of pathologic response will be reported for the study.
Time frame: Up to 10 years
Objective response rate (ORR) defined as the proportion of subjects who achieved a complete response (disappearance of all target tumors) or a partial response (>= 30% decrease in the sum of the longest diameters of target tumors)
Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The ORR, along with exact two-sided 95% confidence intervals, will be reported for the study.
Time frame: Up to 10 years
Recurrence-free survival rate
Median recurrence-free survival with 95% confidence interval (CI) and survival rates at 2, 5 and 10 years will be estimated using the Kaplan-Meier method for both local and distant recurrence.
Time frame: Up to 10 years
Overall survival rate
Median overall survival with 95% CI and survival rates at 2, 5 and 10 years will be estimated using Kaplan-Meier method.
Time frame: Up to 10 years
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