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

NCT02171260 | Completed Phase 1 Results FDA Drug

• 1 other identifier: E7389-A001-113 (ADVL1314)
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 18

Brief 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. 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.

Conditions

Pediatrics; Solid Tumors

Keywords

Tumors; Lymphomas; Solid Tumors; Pediatric

Outcome Measures

Primary Outcomes (12)

• 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.

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

• 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.

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

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

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

• Number of Participants With Clinically Significant Vital Sign Values

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

• Number of Participants With Clinically Significant Electrocardiogram (EKG)

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

• T1/2: Terminal Half-life for Eribulin Mesylate

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

• Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate

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

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

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

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

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

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

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

• CL: Clearance for Eribulin Mesylate

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

• Vd: Volume of Distribution for Eribulin Mesylate

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

Secondary Outcomes (1)

• Number of Participants With Best Overall Response

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

Study Arms (1)

Eribulin Mesylate

EXPERIMENTAL

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 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.

Drug: Eribulin Mesylate

Interventions

Eribulin Mesylate DRUG

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

Also known as: E7389

Eribulin Mesylate

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Eisai Inc.: lead
• Children's Oncology Group: collaborator

Study Sites (18)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Cancer Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 1914, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98145, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Neoplasms; Lymphoma

Interventions

eribulin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

In Part A2, the study was open for the enrolment of infant participants of less than 12 months of age, however no participants were enrolled into this part.

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 24, 2014
• Study Start: July 31, 2014
• Primary Completion: January 28, 2016
• Study Completion: January 28, 2016
• Last Updated: January 15, 2019
• Results First Posted: December 24, 2018

Record last verified: 2018-06

Locations

US (18)