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Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma

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ClinicalTrials.gov Identifier: NCT02097238
Recruitment Status : Completed
First Posted : March 27, 2014
Results First Posted : September 1, 2017
Last Update Posted : September 1, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies how well eribulin mesylate works in treating patients with osteosarcoma that has come back after treatment (recurrent) or has not responded to treatment (refractory). Microtubule inhibitors, such as eribulin mesylate, may stop or slow the growth of tumor cells by disrupting the cell cycle.

Condition or disease Intervention/treatment Phase
Recurrent Osteosarcoma Drug: Eribulin Mesylate Other: Pharmacological Study Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the 4 month progression free survival rate and objective response rate in patients with recurrent osteosarcoma who are administered eribulin (eribulin mesylate) therapy on day 1 and day 8 of 21 day cycles.

SECONDARY OBJECTIVES:

I. To investigate the pharmacokinetics (PK) of eribulin in subjects with recurrent osteosarcoma.

II. To further describe the tolerability of single agent eribulin.

OUTLINE:

Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 5 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Eribulin (NSC# 707389) in Recurrent or Refractory Osteosarcoma
Study Start Date : August 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (eribulin mesylate)
Patients receive eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Drug: Eribulin Mesylate
Given IV
Other Names:
  • E7389
  • ER-086526
  • Halaven
  • Halichondrin B Analog

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Disease Control Success [ Time Frame: Four Months following enrollment on the study ]
    The number of patients who do not experience disease progression or death in the four months following enrollment on AOST1322.

  2. RECIST Response [ Time Frame: First 5 cycles of protocol therapy ]
    The number of patients who experience a complete or partial response according the the RECIST criteria as defined in Eisenhauer et al. Eur J Cancer 45:228-47, 2009.


Secondary Outcome Measures :
  1. Number of Cycles Where a Dose Limiting Toxicity Was Identified [ Time Frame: 39 cycles were considered for this analysis ]
    Each cycle where the patient receives eribulin and does not receive nonprotocol anticancer therapy will be considered in the analysis. A dose limiting toxicity is defined to be: Day 8 eribulin dose is held due to Grade 3 or Grade 4 nonhematological toxicity attributable to the investigational drug and does not resolve to meet eligibility or baseline criteria by Day 11. Any ≥ Grade 3 nonhematological toxicity attributable to the investigational drug with the specific exclusion of: Grade 3 nausea and vomiting < 3 days duration Grade 3 liver enzyme elevation, including ALT/AST/GGT, that returns to Grade ≤ 1 or baseline prior to the time for the next treatment cycle.

  2. PK Parameters of Eribulin Mesylate [ Time Frame: Per Cycle Incidence of dose limiting toxicity. ]
    Data from all patients who provide samples for pharmacokinetic analysis will be aggregated. The sample mean and variance of the area under the curve, clearance and half-life will be calculated. The analytic unit for monitoring for excessive toxicity will be the patient-cycle: Each cycle where the patient receives eribulin and does not receive non-protocol anticancer therapy will be considered in the analysis.



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Ages Eligible for Study:   12 Years to 49 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have had histologic verification of osteosarcoma at original diagnosis
  • Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria, and have relapsed or become refractory to conventional therapy
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have a life expectancy of >= 8 weeks
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    • Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
    • Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
    • Bisphosphonates: at least 4 weeks since the completion of therapy with a bisphosphonate
    • Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
    • Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 75,000/uL (transfusion independent)
  • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
  • A serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR)

    • Age (12 to < 13 years) - serum creatinine of 1.2 mg/dL
    • Age (13 to < 16 years) - serum creatinine of 1.5 mg/dL (male) and 1.4 mg/dL (female)
    • Age (>= 16 years) - serum creatinine of 1.7 mg/dL (male) and 1.4 mg/dL (female)
  • Bilirubin (sum of conjugate + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 units per liter (U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin > 2 g/dL
  • Shortening fraction of >= 27% by echocardiogram
  • Ejection fraction of >= 50% by radionuclide angiogram
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with congenital prolonged QT syndrome
  • Patients with a baseline QT/corrected QT (QTc) interval >= 501 msec
  • Patients who are receiving drugs that prolong the QTc are not eligible
  • Patients who have previously received eribulin, halichondrin B, or analogues of halichondrin B
  • Patients who have grade >= 2 peripheral neuropathy
  • Patients who are receiving other cancer directed therapy at the time of enrollment
  • Patients who have had major surgery within 3 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery
  • Pregnancy and breast feeding

    • Female patients who are pregnant are ineligible
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants
    • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
    • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

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): NCT02097238


  Show 119 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Michael Isakoff Children's Oncology Group

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02097238     History of Changes
Other Study ID Numbers: NCI-2014-00621
NCI-2014-00621 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-AOST1322
AOST1322 ( Other Identifier: Children's Oncology Group )
AOST1322 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: March 27, 2014    Key Record Dates
Results First Posted: September 1, 2017
Last Update Posted: September 1, 2017
Last Verified: July 2017

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