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Trial record 25 of 157 for:    eribulin

Study to Assess Safety and Preliminary Activity of Eribulin Mesylate in Pediatric Participants With Relapsed/Refractory Rhabdomyosarcoma (RMS), Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) and Ewing Sarcoma (EWS)

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ClinicalTrials.gov Identifier: NCT03441360
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
This study will be conducted as an assessment of the safety and preliminary activity of eribulin mesylate in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS) to determine whether each cohort warrants further investigation.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Rhabdomyosarcoma Non-rhabdomyosarcoma Soft Tissue Sarcoma Ewing Sarcoma Drug: Eribulin mesylate Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-label Study to Assess Safety and Preliminary Activity of Eribulin Mesylate in Pediatric Subjects With Relapsed/Refractory Rhabdomyosarcoma (RMS), Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) and Ewing Sarcoma (EWS)
Actual Study Start Date : April 17, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020


Arm Intervention/treatment
Experimental: Eribulin mesylate 1.4 mg/m^2: RMS
Pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS) will receive eribulin mesylate administered as an intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 milligrams per meters squared (mg/m^2). Participants will continue study therapy until progression of disease (per Response Evaluation Criteria In Solid Tumors [RECIST] 1.1), intolerable toxicity, or withdrawal of consent.
Drug: Eribulin mesylate
Intravenous infusion

Experimental: Eribulin mesylate 1.4 mg/m^2: NRSTS
Pediatric participants with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) will receive eribulin mesylate administered as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m^2. Participants will continue study therapy until progression of disease (per RECIST 1.1), intolerable toxicity, or withdrawal of consent.
Drug: Eribulin mesylate
Intravenous infusion

Experimental: Eribulin mesylate 1.4 mg/m^2: EWS
Pediatric participants with Ewing sarcoma (EWS) will receive eribulin mesylate administered as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m^2. Participants will continue study therapy until progression of disease (per RECIST 1.1), intolerable toxicity, or withdrawal of consent.
Drug: Eribulin mesylate
Intravenous infusion




Primary Outcome Measures :
  1. Objective response [ Time Frame: up to 36 months ]
    Number of participants achieving a best objective response of partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, by up to 24 weeks after all participants have completed response assessment. Response assessment will be as determined by investigator. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: up to 36 months ]
    PFS is defined as the time from the first dose date to the date of disease progression (PD) or date of death (whichever occurs first). PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  2. Number of participants with any treatment-emergent (TE) serious adverse event (SAE) [ Time Frame: up to 36 months ]
    An SAE is any untoward medical occurrence that at any dose: results in death; is life threatening (ie, the participant was at immediate risk of death from the adverse event as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). A treatment-emergent adverse event (TEAE) is defined as an AE that emerges during treatment, having been absent at pretreatment (Baseline) or (1) reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or (2) worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.

  3. Number of participants with any TE non-serious adverse event [ Time Frame: up to 36 months ]
    An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with the medicinal product. A TEAE is defined as an AE that emerges during treatment, having been absent at pretreatment (Baseline) or (1) reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or (2) worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.

  4. Number of participants with any abnormal, clinically significant clinical laboratory value [ Time Frame: up to 36 months ]
    Clinical significance will be assessed by the investigator.

  5. Number of participants with any abnormal, clinically significant electrocardiogram (ECG) value [ Time Frame: up to 36 months ]
    Clinical significance will be assessed by the investigator.

  6. Number of participants with any abnormal, clinically significant vital sign value [ Time Frame: up to 36 months ]
    Clinical significance will be assessed by the investigator.

  7. Change from Baseline in scores on the Lansky Play-Performance Scale [ Time Frame: Baseline; up to 36 months ]
    The Lansky Play-Performance Scale can be used to rate a child's activity level. Parents will be asked to rate their child's activity level over the past week. Scores on the Lansky Play-Performance Scale range from 0 (unresponsive) to 100 (fully active, normal).

  8. Change from Baseline in Karnofsky Performance Status Scores [ Time Frame: Baseline; up to 36 months ]
    The Karnofsky Performance scale allows physicians to classify participants based on functional impairment. Physicians will assign a performance score for participants, ranging from 0 (dead) to 100 (normal, no complaints).

  9. Duration of Response (DOR) [ Time Frame: From day of first documentation of PR or CR to the day of disease progression or death (up to 36 months) ]
    DOR is defined as the time from the first date of documented PR or CR to the date of disease progression or date of death (whichever occurs first). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  10. Overall Survival (OS) [ Time Frame: From the day of first dose to the day of death (up to 36 months) ]
    OS is defined as the time from the first dose date to the date of death.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: ≥12 months to <18 years old at the time of informed consent
  • Diagnosis: Histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) (Grade 2 or 3), or Ewing sarcoma (EWS) which is relapsed or refractory (failed front line therapy)
  • The presence of measurable disease meeting the following criteria:

    • At least 1 lesion of ≥1.0 centimeter (cm) in the longest diameter for a non-lymph node or ≥1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI).
    • Lesions that have had radiotherapy must show subsequent radiographic evidence of increase in size by at least 20% to be deemed a target lesion.
  • Therapeutic options: Participant's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
  • Performance level: Performance score ≥50%. Karnofsky (for participants >16 years of age) or Lansky (for participants ≤16 years of age). Participants who are unable to walk because of paralysis and/or previous surgeries, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
  • Participants must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to study drug administration. If, after the required time frame, the numerical eligibility criteria are met, eg, blood count criteria, the participant is considered to have recovered adequately:

    • Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
    • Anticancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count [ANC] counts): ≥7 days after the last dose of agent.
    • Monoclonal antibodies ≥ 3 half-lives must have elapsed from infusion of last dose of antibody (including checkpoint inhibitors), and toxicity related to prior antibody therapy must be recovered to Grade ≤1.
    • Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor (eg, Neulasta) or 7 days for a short-acting growth factor. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor.
    • Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ≥21 days after the completion of interleukins, interferons, or cytokines (other than hematopoietic growth factors)
    • Stem cell infusions (with or without total body irradiation [TBI]): ≥84 days
    • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion or boost infusion: ≥84 days after infusion and no evidence of graft versus host disease (GVHD)
    • Autologous stem cell infusion including boost infusion: ≥42 days
    • Cellular therapy: ≥42 days after the completion of any type of cellular therapy (eg, modified T-cells, natural killer cells, dendritic cells, etc)
    • Radiation therapy (XRT)/External Beam Irradiation including Protons: ≥14 days after local XRT; ≥150 days after TBI, craniospinal XRT or if radiation to ≥50% of the pelvis; ≥42 days if other substantial BM radiation
    • Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I-metaiodobenzylguanidine): ≥42 days after systemically administered radiopharmaceutical therapy.
  • Adequate bone marrow function, defined as:

    • ANC ≥1.0 × 10^9/Liter (L)
    • Platelet count ≥100 × 10^9/L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to study drug administration)
    • Hemoglobin at least 8.0 grams per deciliter (g/dL) at Baseline (blood transfusions are allowed during the screening period to correct hemoglobin values less than 8.0 g/dL) Note: As blood transfusions are permitted to meet the hemoglobin criteria, participants requiring transfusion must not be known to be refractory to red blood cell or platelet transfusions.
  • Adequate renal function, defined as:

    • A serum creatinine based on age/gender, derived from the Schwartz formula for estimating glomerular filtration rate (GFR)
    • Or creatinine clearance or GFR ≥50 milliliters per minute (mL/min)/1.73 meters squared (m^2) based on a 12 or 24 hour urine creatinine collection
  • Adequate liver function, defined as:

    • Bilirubin (sum of conjugated + unconjugated) ≤1.5 × upper limit of normal (ULN) for age
    • Alanine aminotransferase (ALT) ≤110 units per Liter (U/L). For the purpose of this study, the ULN for ALT is 45 U/L
    • Serum albumin ≥2 g/dL
  • Informed consent: All participants and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Participants must be willing to comply with all aspects of the protocol.

Exclusion Criteria:

  • Pregnancy, breastfeeding, contraception: Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic [β-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

    • Females of childbearing potential (all post pubertal females will be considered to be of childbearing potential unless they have early menopause [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing]) who:
    • Do not agree to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation, ie:
    • Total abstinence (if it is their preferred and usual lifestyle);
    • An intrauterine device (IUD) or intrauterine system (IUS);
    • A contraceptive implant;
    • An oral contraceptive (must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study and for 6 months after study drug discontinuation); or
    • Do not have a vasectomized partner with confirmed azoospermia.

For sites outside of the European Union (EU), it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, or the participant has commenced/adjusted/changed oral hormonal contraceptive product/dose within 4 weeks prior to study drug administration, then the participant must agree to use a medically acceptable method of contraception, ie, double barrier methods of contraception such as condoms plus diaphragm or cervical/vault cap with spermicide.

  • Males who have not had a successful vasectomy (confirmed azoospermia) or if they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period or for 3 months after study drug discontinuation). No sperm donation is allowed during the study period or for 3 months after study drug discontinuation.

    - Concomitant medications:

  • Corticosteroids: Participants receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to study drug administration (except when indicated for Central Nervous System [CNS] metastases, then participants must not have received corticosteroids for at least 28 days)
  • Anticancer Agents: participants who are currently receiving other anticancer agents
  • Anti-GVHD agents Post-transplant: Participants who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant
  • Strong CYP3A4 inducers/inhibitors

    • Received prior therapy with eribulin mesylate
    • Any other malignancy that required treatment (except for non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ), within 2 years prior to study drug administration
    • Has hypersensitivity to eribulin or any of the excipients
    • Has a prior history of viral hepatitis (B or C) as demonstrated by positive serology (presence of antigens) or have an uncontrolled infection requiring treatment. Participants with a known prior history of hepatitis B or C may be eligible pending agreement with the sponsor.
    • Has > Grade 1 peripheral sensory neuropathy or > Grade 1 peripheral motor neuropathy graded according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies
    • Has cardiac pathology: Participants with known congestive heart failure, symptomatic or left ventricular (LV) ejection fraction <50% or shortening fraction <27%
    • Participants with congenital long QT syndrome, bradyarrhythmias, or QTc >480 msec on at least 2 separate electrocardiograms (ECGs).
    • Has CNS Disease: Participants with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy (eg, surgery or radiotherapy) and have discontinued the use of corticosteroids for this indication for at least 4 weeks prior to study drug administration. Confirmation of radiographic stability must be done by comparing the brain scan (CT or MRI) performed during the Screening Period, using the same imaging modality, to a brain scan performed earlier (and following local therapy where applicable). Participants must be clinically stable. It is not the intention of this protocol to treat participants with active brain metastases.

Note: CNS imaging is required to confirm eligibility for participants with a known history of CNS disease.

  • Have had or are planning to have the following invasive procedures:

    • Major surgical procedure or significant traumatic injury within 28 days prior to study drug administration
    • Laparoscopic procedure or open biopsy within 7 days prior to study drug administration
    • Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 2 days prior to study drug administration
    • Core biopsy, including bone marrow biopsy, within 2 days prior to study drug administration
    • Fine needle aspirate within 3 days prior to study drug administration
  • Has any serious concomitant illness that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
  • Participants with known human immunodeficiency virus (HIV); due to lack of available safety data for eribulin therapy in HIV-infected participants

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): NCT03441360


Contacts
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Contact: Eisai Medical Information 1-888-274-2378 esi_oncmedinfo@eisai.com

  Show 40 Study Locations
Sponsors and Collaborators
Eisai Inc.

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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03441360     History of Changes
Other Study ID Numbers: E7389-G000-223
First Posted: February 21, 2018    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:
eribulin mesylate
pediatric

Additional relevant MeSH terms:
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Sarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Myosarcoma
Neoplasms, Muscle Tissue
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue