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This is a Phase 1 Study of Eribulin Mesylate in Pediatric Patients With Recurrent or Refractory Solid Tumors (Excluding CNS), Including Lymphomas. (BOLD 113)

This study is currently recruiting participants.
Verified October 2016 by Eisai Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02171260
First Posted: June 24, 2014
Last Update Posted: November 1, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Eisai Inc.
  Purpose
This is a Phase 1 study of eribulin mesylate in pediatric patients with recurrent or refractory solid tumors (excluding CNS), including lymphomas. Eribulin mesylate will be administered intravenously, once per day on Days 1 and 8 of a 21-day cycle. This study aims to determine the MTD and/or the RP2D of this regimen in Part A1 (patients greater than or equal to 12 months and less than 18 years). Part A2 will enroll infants (greater than 6 months and less than 12 months) one dose level behind the dose level at which patients in Part A1 are enrolling, in order to maximize safety for infant subjects. Additionally, this study aims to describe the toxicities and the pharmacokinetics of eribulin mesylate when administered to children. In a preliminary manner, the antitumor effect of eribulin mesylate will also be described.

Condition Intervention Phase
Pediatrics Solid Tumors Drug: Eribulin Mesilate Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of eribulin mesylate administered as an intravenous infusion [ Time Frame: Days 1 and 8 of a 21-day cycle ]
  • Number of Adverse events as assessed by CTCAE version 4.0, as a measure of safety and tolerability [ Time Frame: Up to 5 days ]
    All adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All graded adverse events will be routinely reported throughout the study. Analysis will determine the maximum tolerable dose, and the describe the toxicity profile for the pediatric solid tumor patients.

  • Pharmacokinetics of eribulin mesylate: Cmax [ Time Frame: Up to 5 days ]
    For subjects greater than or equal to 12 months and less than 18 years of age, Cmax will be determined after the first dose of eribulin. Additionally, after the second dose of eribulin, C0.083 hr will be determined and descriptively compared to the first dose Cmax (and first dose C0.083 hr).

  • Pharmacokinetics of eribulin mesylate: tmax [ Time Frame: Up to 5 days ]
    For subjects greater than or equal to 12 months and less than 18 years of age, tmax will be determined after the first dose of eribulin.

  • Pharmacokinetics of eribulin mesylate: AUC [ Time Frame: Up to 5 days ]
    For subjects greater than or equal to 12 months and less than 18 years of age, AUC will be determined after the first dose of eribulin.


Secondary Outcome Measures:
  • Evaluation of disease response to preliminarily define the antitumor activity of eribulin [ Time Frame: Up to 5 days ]
    Patients will have tumor disease evaluations performed at the end of cycles 1, 3, and 5 and then every 3 cycles. Disease response will be assessed according to RECIST 1.1 criteria for patients with solid tumors and will be reported descriptively. Analyses will be descriptive and exploratory and hypotheses generating in nature.

  • Pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer: Cmax [ Time Frame: Up to 5 days ]
    For subjects greater than 6 months but less than 12 months of age, Cmax will be determined after the first dose of eribulin. Additionally, after the second dose of eribulin, C0.083 hr will be determined and descriptively compared to the first dose Cmax (and first dose C0.083 hr).

  • Pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer: tmax [ Time Frame: Up to 5 days ]
    For subjects greater than 6 months but less than 12 months of age, tmax will be determined after the first dose of eribulin.

  • Pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer: AUC [ Time Frame: Up to 5 days ]
    For subjects greater than 6 months but less than 12 months of age, AUC will be determined after the first dose of eribulin.


Estimated Enrollment: 23
Study Start Date: July 2014
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E7389
Eribulin mesylate will be administered intravenously on Days 1 and 8 of each 21-day cycle. A cycle of therapy is considered to be 21 days. The starting dose for eribulin mesylate will be at 1.1 mg/m2 (Dose Level 1), which is approximately 80% of the adult maximum tolerated dose (MTD), and will be escalated up to no more than 2.2 mg/m2.
Drug: Eribulin Mesilate
Eribulin mesylate will be administered intravenously on Days 1 and 8 of each 21-day cycle.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients must be greater than or equal to 12 months and less than 18 years of age at the time of study enrollment.
  • Patients must be greater than 6 months and less than 12 months of age at the time of study enrollment. Patients will enroll one dose level behind the dose level at which patients in Part A1 are enrolling.
  • Patients with refractory or recurrent solid tumors or lymphomas, excluding CNS tumors, are eligible. Patients must have had histologic -verification of malignancy at original diagnosis or relapse. Patients with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligible.
  • Patients must have either measurable or evaluable disease.
  • Patient'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.
  • Karnofsky greater than or equal to 50% for patients greater than 16 years of age and Lansky greater than or equal to 50 for patients less than or equal to 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Patients must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy.

    1. Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
    2. Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
    3. Biologic (anti-neoplastic agent): At least 14 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
    4. Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
    5. Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
    6. XRT: At least 14 days after local palliative XRT (small port); At least 150 days must have elapsed if prior TBI, craniospinal and/or entire spinal XRT or if greater than or equal to 50% radiation of pelvis; At least 42 days must have elapsed if other substantial BM radiation.
    7. Stem Cell Infusion without TBI: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion.
  • Adequate Bone Marrow Function Defined as:
  • Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/mm^3
  • Platelet count greater than or equal to 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
  • Hemoglobin (Hb) at least 8 g/dL at baseline (blood transfusions are allowed during the screening period to correct Hb values less than 8g/dL).
  • All patients enrolled on the study must be evaluable for hematologic toxicity.
  • Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m^2 or
  • A serum creatinine based on age/gender as follows:

Maximum Serum Age Creatinine (mg/dL)

Male Female

6 months to less than 1 year 0.5 0.5

  1. to less than 2 years 0.6 0.6
  2. to less than 6 years 0.8 0.8

6 to less than 10 years 1 1 10 to less than 13 years 1.2 1.2 13 to less than 16 years 1.5 1.4 greater than 16 years 1.7 1.4

The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.

  • Bilirubin (sum of conjugated unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) less than or equal to 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
  • SGOT (AST) less than or equal to 125 U/L. For the purpose of this study, the ULN for SGOT is 50 U/L.
  • Serum albumin greater than or equal to 2 g/dL.
  • Shortening fraction of greater than or equal to 27% by echocardiogram, or ejection fraction of greater than or equal to 50% by gated radionuclide study.
  • QTc less than or equal to 480 msec. Note: Patients with Grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e. electrolytes, medications). See Appendix II for a list of drugs that prolong QTc.
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Patients must be willing to comply with all aspects of the protocol.
  • Patients with known human immunodeficiency virus (HIV) who have CD4 T cell counts greater than or equal to 500 cells/mm3 and who do not require antiretroviral therapy are eligible.

Exclusion Criteria

  • Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective double barrier contraceptive method for the entire period in which they are receiving protocol therapy.
  • Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
  • Patients who are currently receiving another investigational drug are not eligible.
  • Patients who are currently receiving other anticancer agents are not eligible.
  • Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
  • Patients who are receiving drugs that prolong the QTc are not eligible.
  • Patients who have received prior therapy with eribulin mesylate are not eligible.
  • Patients with hypersensitivity to excipients of the study drug are not eligible. The excipients are ethanol, hydrochloric acid, sodium hydroxide and water for injection.
  • Patients who have a prior history of viral hepatitis (B or C) as demonstrated by positive serology (presence of antigens) or have an uncontrolled infection requiring treatment are not eligible.
  • Patients with greater than Grade 1 peripheral sensory neuropathy or greater than Grade 1 peripheral motor neuropathy graded according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies are not eligible.
  • Patients with known congestive heart failure, symptomatic or LV ejection fraction 50% or shortening fraction less than 27% are not eligible.
  • Patients with congenital long QT syndrome, bradyarrhythmias, or QTc greater than 480 msec are not eligible.
  • Patients with primary CNS tumors are not eligible.
  • Patients with prior history of or known metastatic CNS disease involvement are not eligible. (Note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated).
  • Patients who have had or are planning to have the following invasive procedures are not eligible:
  • Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment.
  • Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g. Hickman or Broviac) and at least 7 days prior to enrollment for subcutaneous port.
  • Core biopsy within 7 days prior to enrollment.
  • Fine needle aspirate within 7 days prior to enrollment.
  • Patients with known bone marrow involvement are not eligible.
  • Patients who have received a prior solid organ transplantation are not eligible.
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
  Contacts and Locations
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): NCT02171260


Contacts
Contact: Eisai Medical Services 1-888-422-4743

  Show 21 Study Locations
Sponsors and Collaborators
Eisai Inc.
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02171260     History of Changes
Other Study ID Numbers: E7389-A001-113 (ADVL1314)
First Submitted: June 18, 2014
First Posted: June 24, 2014
Last Update Posted: November 1, 2016
Last Verified: October 2016

Keywords provided by Eisai Inc.:
Tumors
Lymphomas
Solid Tumors
Pediatric