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)

NCT03441360 | Completed Phase 2 Results FDA Drug

• 1 other identifier: E7389-G000-223
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 41

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.

Conditions

Relapsed/Refractory Rhabdomyosarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma; Ewing Sarcoma

Keywords

eribulin mesylate; pediatric

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Objective Response

  Percentage of participants achieving a best objective response of partial response (PR) or complete response (CR) per RECIST 1.1, by up to 24 weeks after all participants have completed response assessment. Response assessment was determined by investigator. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From date of randomization up to first documentation of disease progression (PD) or date of death, whichever occurred first (approximately 32 months)

Secondary Outcomes (9)

• Progression-free Survival (PFS)

  From the time from the first dose date to the date of disease progression (PD) or date of death, whichever occurred first (up to approximately 32 months)

• Number of Participants With Any Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)

• Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value

  From first dose of study drug up to approximately 32 months

• Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values

  From first dose of study drug up to approximately 32 months

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values

  From first dose of study drug up to approximately 32 months

Study Arms (3)

Eribulin mesylate 1.4 mg/m^2: RMS

EXPERIMENTAL

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

Eribulin mesylate 1.4 mg/m^2: NRSTS

EXPERIMENTAL

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

Eribulin mesylate 1.4 mg/m^2: EWS

EXPERIMENTAL

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

Interventions

Eribulin mesylate DRUG

Intravenous infusion

Eribulin mesylate 1.4 mg/m^2: EWS; Eribulin mesylate 1.4 mg/m^2: NRSTS; Eribulin mesylate 1.4 mg/m^2: RMS

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (41)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Loma Linda University Cancer Center

Loma Linda, California, 92350, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Southern California Permanente Medical Group

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hospital- San Diego

San Diego, California, 92123, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Nemours / A.I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

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

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, 46202, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

CS Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospital and Clinics

Kansas City, Missouri, 64108, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers cancer Institute of NJ

New Brunswick, New Jersey, 08853, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Randall Children's Hospital at Legacy Emanuel

Portland, Oregon, 97227, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Penn State Health Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

Location

Children's Hosptial of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing

Interventions

eribulin

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Results Point of Contact

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

esi_oncmedinfo@eisai.com

+1-888-274-2378

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: February 22, 2018
• Study Start: April 17, 2018
• Primary Completion: January 7, 2021
• Study Completion: January 21, 2022
• Last Updated: October 5, 2022
• Results First Posted: January 28, 2022

Record last verified: 2022-01

Locations

US (41)