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Trial record 96 of 157 for:    eribulin

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

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ClinicalTrials.gov Identifier: NCT03361436
Recruitment Status : Recruiting
First Posted : December 4, 2017
Last Update Posted : June 25, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Lara Davis, OHSU Knight Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Liposarcoma Retroperitoneal Neoplasm Drug: Eribulin Mesylate Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Procedure: Quality-of-Life Assessment Other: Questionnaire Administration Procedure: Therapeutic Conventional Surgery Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

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 course 1. Treatment repeats every 21 days for up to 3 courses 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1B Trial of Preoperative Eribulin and Radiation for Retroperitoneal Liposarcoma
Actual Study Start Date : March 19, 2018
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2022


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 course 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo surgery within 3-10 weeks after radiation therapy.
Drug: Eribulin Mesylate
Given IV
Other Names:
  • B1939 Mesylate
  • E7389
  • ER-086526
  • Halaven
  • Halichondrin B Analog

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Procedure: Therapeutic Conventional Surgery
Undergo surgery




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 [ Time Frame: Up to 42 days ]
    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.


Secondary Outcome Measures :
  1. Change in subject-reported quality of life assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: Baseline up to 9 weeks after surgery ]
    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).

  2. 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) [ Time Frame: Up to 10 years ]
    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.

  3. Overall survival rate [ Time Frame: Up to 10 years ]
    Median overall survival with 95% CI and survival rates at 2, 5 and 10 years will be estimated using Kaplan-Meier method.

  4. Pathologic response defined as the percentage of tumor with treatment change, including necrosis, fat maturation and hyalinization [ Time Frame: Up to 10 years ]
    Descriptive statistics including mean, median, standard deviation, and 95% confidence interval of pathologic response will be reported for the study.

  5. Rate of early surgical resection [ Time Frame: 3 weeks after radiation therapy ]
    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.

  6. Rate of enrollment [ Time Frame: Up to 18 months ]
  7. Rate of R0 resection defined as the proportion of surgical specimens with microscopically negative margins [ Time Frame: Up to 10 years ]
    The rate of R0 resection, along with exact two-sided 95% confidence intervals, will be reported for the study.

  8. Rate of serious post-operative complications [ Time Frame: Up to 9 weeks following surgery ]
    This rate, along with exact two-sided 95% confidence intervals, will be reported for the study.

  9. Rate of surgical resection [ Time Frame: Beyond 10 weeks of radiation ]
    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.

  10. Recurrence-free survival rate [ Time Frame: Up to 10 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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
  • 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

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 congenital long QT syndrome or torsades de pointes
  • 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; breastfeeding should be discontinued
  • Unable or unwilling to stop the use of herbal supplements; the use of marijuana or its derivatives is allowed; the use of nutritional supplements may be allowed after review by a study pharmacist to confirm no significant risk of interaction with eribulin or radiation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03361436


Locations
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United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Lara E. Davis    503-494-8423    davisla@ohsu.edu   
Principal Investigator: Lara E. Davis         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Lara Davis OHSU Knight Cancer Institute

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Responsible Party: Lara Davis, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT03361436     History of Changes
Other Study ID Numbers: STUDY00017190
NCI-2017-02120 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
STUDY00017190 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( U.S. NIH Grant/Contract )
First Posted: December 4, 2017    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

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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

Additional relevant MeSH terms:
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Liposarcoma
Retroperitoneal Neoplasms
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Abdominal Neoplasms
Neoplasms by Site
Halichondrin B
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents