Eribulin and Radiation Therapy in Treating Patients With Retroperitoneal Liposarcoma That Can Be Removed by Surgery

A Phase 1B Trial of Preoperative Eribulin and Radiation for Retroperitoneal Liposarcoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Solid Neoplasm; Liposarcoma; Malignant Abdominal Neoplasm; Malignant Retroperitoneal Neoplasm; Malignant Scrotal Neoplasm; Malignant Spermatic Cord Neoplasm
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Therapeutic Conventional Surgery; Radiation: Intensity-Modulated Radiation Therapy; Drug: Eribulin Mesylate

Detailed Description

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
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically confirmed diagnosis of liposarcoma; all subtypes are eligible
• Sufficient archival tissue available for correlative studies; submission of formalin-fixed paraffin-embedded (FFPE) tumor tissue from a previous biopsy or resection is required, and the most recent specimen is preferred; if a FFPE block cannot be provided, then 10 unstained, positively-charged slides of 4-5 um thickness must be submitted; if insufficient archival tissue is available, a repeat biopsy will be necessary
• Primary or recurrent retroperitoneal, scrotal/spermatic cord or abdominal tumor
• For subjects between the ages of 12-18 years only, body surface area (BSA) must be >= 1.5 m^2
• All sites of disease must be resectable or borderline resectable as assessed by a surgical oncologist with experience in retroperitoneal sarcoma resection after discussion in our institutional multidisciplinary sarcoma tumor board conference
• All sites of disease must be targetable with intensity-modulated radiation therapy (IMRT) with acceptable morbidity and without exceeding normal tissue dose constraints as assessed by a radiation oncologist
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at time of screening
• Fridericia's correction formula (QTcF) interval on standard 12-lead electrocardiography (ECG) parameters at screening (defined as the mean of the triplicate ECGs) of < 450 msec for males and < 470 msec for females
• Ejection fraction of >= 50%
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Individuals of childbearing potential must be willing to use adequate contraception throughout the study and for 3 weeks after study drug discontinuation
• Absolute neutrophil count (ANC) >= 1 K/cu mm
• Platelets (no transfusion within prior 7 days) >= 100 K/cu mm
• Hemoglobin (no transfusion within prior 7 days) >= 9.0 g/dL
• Total bilirubin < institutional upper limit of normal (ULN), except for subjects with documented Gilbert's syndrome, for which =< 3.0 x ULN or direct bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
• Estimated creatinine clearance > 50 mL/min by Cockcroft-Gault equation
• Ability to understand and the willingness to sign a written informed consent document; subject has signed the informed consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements

Exclusion Criteria:

• Presence of distant metastases; intra-abdominal (regional) spread is allowable if meets inclusion criterial indeterminate or small volume pulmonary nodules may be eligible, if the treating physicians recommend curative-intent resection of the primary tumor despite the presence of possible lung metastases
• Prior radiation or systemic therapy for the diagnosis of liposarcoma
• Prior eribulin
• Grade >= 2 peripheral neuropathy
• Contraindication to magnetic resonance imaging (MRI), including presence of a pacemaker or aneurysm clip, severe claustrophobia, a known reaction to gadolinium contrast, or body weight exceeding 300 pounds (lbs)
• Concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of malignancies that have completed therapy and are considered by their physician to be at less than 30% risk of relapse; prior systemic therapy is allowed with the exception of prior eribulin; prior radiation therapy is allowed with the exception of any abdominal, pelvic or retroperitoneal radiation > 10 Gy
• History of uncontrolled arrhythmia, congenital long QT syndrome or torsades de pointes (TdP)
• Use of more than one medication with a known risk of TdP
• Major operation within 14 days prior to starting study drug or not recovered from surgical complications; neither tumor biopsy nor central line insertion are considered a major operation
• Active infection; any systemic antimicrobial therapy must be completed >= 5 days prior to initiation of protocol therapy
• Pregnant or nursing (lactating) individuals; NOTE: Pregnant individuals are excluded from this study because eribulin is an investigational agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the individual with eribulin breastfeeding should be discontinued; these potential risks may also apply to doxorubicin
• Unable or unwilling to stop the use of herbal supplements; the use of marijuana or its derivatives is allowed; the use of supplements may be allowed after review by a study pharmacist to confirm no significant risk of interaction with eribulin or radiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (eribulin mesylate, IMRT, surgery); Patients receive eribulin mesylate IV over 2-5 minutes on days 1 and 8 and undergo intensity-modulated radiation therapy 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Drug: Eribulin Mesylate; Given IV; Other Names: Halaven; E7389; ER-086526; B1939 Mesylate; Halichondrin B Analog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of enrollment		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.	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.	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).	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.	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.	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.	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.	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.	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.	Up to 10 years

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: Oregon Health and Science University; Eisai Inc.
• Investigators: Principal Investigator: Lara E Davis, OHSU Knight Cancer Institute

Publications and helpful links

General Publications

• Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Actual): February 14, 2023
• Study Completion (Estimated): April 14, 2033

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: November 28, 2017
• First Posted (Actual): December 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Adipose Tissue; Liposarcoma; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy, Intensity-Modulated; eribulin
• Other Study ID Numbers: STUDY00017190 (Other Identifier: OHSU Knight Cancer Institute); NCI-2017-02120 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No