Eribulin Mesylate and Radiation Therapy in Treating Patients with Retroperitoneal Liposarcoma That Can Be Removed by Surgery
- 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
- Female 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%)
- Men and women 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
- 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) women; NOTE: Pregnant women 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 mother 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
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.
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.
Trial Phase Phase I
Trial Type Treatment
OHSU Knight Cancer Institute
Lara E. Davis
- Primary ID STUDY00017190
- Secondary IDs NCI-2017-02120
- Clinicaltrials.gov ID NCT03361436