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PediatricsPhase 1BOLD 113NCT02171260

This is a Phase 1 Study of Eribulin Mesylate in Pediatric Participants With Recurrent or Refractory Solid Tumors (Excluding [Central Nervous System] CNS), Including Lymphomas

A Phase 1 study testing Eribulin Mesylate in people with Pediatrics and Solid Tumors, run by Eisai Inc. at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase 1 study of eribulin mesylate in pediatric participants 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. Read more about this study

Who is it for?
Ages 6 months to 17 years
Conditions the study is for
Pediatrics, Solid Tumors
What is being tested?
Eribulin Mesylate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
18 sitesUnited States
Study dates
31 Jul 2014to 28 Jan 2016
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Participants must be >=12 months and <18 years of age at the time of study enrollment (Part A1).
  • Participants must be >6 months and <12 months of age at the time of study enrollment (Part A2). Participants will enroll one dose level behind the dose level at which participants in Part A1 are enrolling.
  • Participants with refractory or recurrent solid tumors or lymphomas, excluding CNS tumors, are eligible. Participants must have had histologic verification of malignancy at original diagnosis or relapse. Participants with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligible.
  • Participants must have either measurable or evaluable disease.
  • Participants 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 >= 50% for participants >16 years of age and Lansky >=50 for participants less than or equal to (<=)16 years of age. Participants 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.
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  • Participants must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy.
  • Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
  • Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (example 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.
  • 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.
  • Immunotherapy: At least 42 days after the completion of any type of immunotherapy, example tumor vaccines.
  • Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
  • X-ray telescope (XRT): At least 14 days after local palliative XRT (small port); At least 150 days must have elapsed if prior total body irradiation(TBI), craniospinal and/or entire spinal XRT or if >=50% radiation of pelvis; At least 42 days must have elapsed if other substantial bone marrow (BM) radiation.
  • Stem Cell Infusion without TBI: No evidence of active graft versus 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) >=1000 per cubic millimeter (/mm^3).
  • Platelet count >=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 gram per deciliter (g/dL) at baseline (blood transfusions are allowed during the screening period to correct Hb values less than 8 g/dL).
  • All participants enrolled on the study must be evaluable for hematologic toxicity.
  • Adequate Renal Function Defined as:
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >=70 milliliter per minute (ml/min) per (/) 1.73 square meter (m^2) or
  • A serum creatinine milligram per deciliter (mg/dL) based on age/gender as follows:
  • 6 months to <1 year: male, 0.5; female, 0.5
  • 1 to < 2 years: male, 0.6; female, 0.6
  • 2 to < 6 years: male, 0.8; female, 0.8
  • 6 to < 10 years: male, 1; female, 1
  • 10 to < 13 years: male, 1.2; female, 1.2
  • 13 to < 16 years: male, 1.5; female, 1.4
  • >=16 years: male, 1.7; female, 1.4
  • The threshold creatinine values were derived from the Schwartz formula for estimating GFR (Schwartz et al., 1985) utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC).
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) <=1.5 * upper limit of normal (ULN) for age
  • serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase [ALT]) <=110 units per liter (U/L). For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) <= 125 U/L. For the purpose of this study, the ULN for SGOT is 50 U/L.
  • Serum albumin >= 2 g/dL
  • Adequate Cardiac Function Defined as:
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
  • Corrected QT interval (QTc) <= 480 millisecond (msec) Note: Participants with Grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (that is, electrolytes, medications).
  • All participants and/or their participants 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.
  • Participants with known human immunodeficiency virus (HIV) who have CD4+ T cell counts greater than or equal to 500 cells/m^3 and who do not require antiretroviral therapy are eligible.

Who cannot join

  • 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 and up to 6 months after treatment.
  • Concomitant Medications
  • Participants 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.
  • Participants who are currently receiving another investigational drug are not eligible.
  • Participants who are currently receiving other anticancer agents are not eligible.
  • Participants who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
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  • Participants who are receiving drugs that prolong the QTc are not eligible.
  • Participants who have received prior therapy with eribulin mesylate are not eligible.
  • Participants with hypersensitivity to excipients of the study drug are not eligible. The excipients are ethanol, hydrochloric acid, sodium hydroxide and water for injection.
  • Participants 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.
  • Participants 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.
  • Cardiac Pathology
  • Participants with known congestive heart failure, symptomatic or left ventricle (LV) ejection fraction 50% or shortening fraction less than 27% are not eligible.
  • Participants with congenital long QT syndrome, bradyarrhythmias, or QTc greater than 480 msec are not eligible.
  • CNS Disease
  • Participants with primary CNS tumors are not eligible.
  • Participants with prior history of or known metastatic CNS disease involvement are not eligible. (Note: CNS imaging for participants without a known history of CNS disease is only required if clinically indicated).
  • Participants 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 (with example, 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. NOTE: For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy.
  • Participants with known bone marrow involvement are not eligible.
  • Participants who have received a prior solid organ transplantation are not eligible.
  • Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • University of Minnesota Cancer Center-Fairview

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center

    New York, New York, 10032

  • Childrens Hospital of Orange County

    Orange, California, 92868

  • Childrens Hospital of Philadelphia

    Philadelphia, Pennsylvania, 1914

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Seattle Children's Hospital

    Seattle, Washington, 98145

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase 1 Study of Eribulin Mesylate, a Novel Microtubule Targeting Chemotherapeutic Agent in Children With Refractory or Recurrent Solid Tumors (Excluding CNS), Including Lymphomas

This is a Phase 1 study of eribulin mesylate in pediatric participants 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 maximum tolerated dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of this regimen in Part A1 (participants greater than or equal to [>=] 12 months and less than [<] 18 years). Part A2 will enroll infants (greater than [>] 6 months and <12 months) one dose level behind the dose level at which participants in Part A1 are enrolling, in order to maximize safety for infant participants. 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.

Being tested
Eribulin Mesylate
Keywords
Tumors, Lymphomas, Solid Tumors, Pediatric
Medical subject headings
Neoplasms, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Eribulin MesylateDrug

    Also called E7389

    Eribulin mesylate will be administered intravenously on Days 1 and 8 of each 21-day cycle.

Study groups in NCT02171260
Study groupRoleWhat they receive
Eribulin MesylateExperimentalEribulin 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 milligram per square meter (mg/m^2) (Dose Level 1), which is approximately 80% of the adult MTD, and will be escalated up to no more than 2.2 mg/m^2.
Receives: Drug: Eribulin Mesylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Eribulin Mesylate

    MTD: maximum dose at which <one third participants had DLT in Cycle 1. DLT: Grade 3/4 drug-related non hematological toxicity (except Grade 3 nausea, vomiting of <3 days, Grade 3 liver enzyme elevation with alanine transaminase/aspartate transaminase and gamma glutamyl transferase that returned to Grade <=1 or baseline prior to next dose; Grade 3 fever, infection, hypophosphatemia, hypokalemia, hypocalcemia/hypomagnesemia responsive to oral supplementation). Non-hematological toxicity causing >=14 days delay between treatment cycles. Haematological DLTs included: Grade 4 neutropenia/platelets<75,000/mm^3 on Day 8 that does not resolve to absolute neutrophil count >=750/mm^3 and platelets>=75,000/mm^3 by Day 11, neutropenia for >7 days; platelet count <25,000/mm^3, or required platelet transfusion, on 2 separate days within 7-day period;Grade 3 thrombocytopenia complicated by bleeding and/or required platelet transfusion;myelosuppression causing >14 days delay between treatment cycles.

    Measured: First dose of study drug (Baseline) up to Cycle 1 Day 21

  2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.

    Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)

  3. Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values

    Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)

  4. Number of Participants With Clinically Significant Vital Sign Values

    Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)

  5. Number of Participants With Clinically Significant Electrocardiogram (EKG)

    Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)

  6. T1/2: Terminal Half-life for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

  7. Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

  8. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

  9. AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

  10. AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

  11. CL: Clearance for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

  12. Vd: Volume of Distribution for Eribulin Mesylate

    Measured: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose

Secondary outcomes (1)

  1. Number of Participants With Best Overall Response

    Best Overall Response (BOR): best response recorded from start of study treatment until disease progression (PD) or recurrence based on response evaluation criteria in solid tumors (RECIST) version 1.1 for target and non-target lesions. Participants with evaluable disease were also eligible for assessment.

    Measured: First dose of study drug (Baseline) up to approximately Cycle 8 (21-days treatment cycle)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2014 (estimated)
  2. Study start31 Jul 2014
  3. Primary completion28 Jan 2016
  4. Study completion28 Jan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02171260
Sponsor's protocol ID
E7389-A001-113 (ADVL1314)
Acronym
BOLD 113
Status last verified
Jun 2018
First submitted
18 Jun 2014
Last updated
15 Jan 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Eribulin Mesylate in people with Pediatrics and Solid Tumors, run by Eisai Inc. at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Eribulin Mesylate (time frame: First dose of study drug (Baseline) up to Cycle 1 Day 21). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02171260.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2019.

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