Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan Hydrochloride in Children With Refractory or Recurrent Solid Tumors

NCT03245450 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: E7389-G000-2132016-003352-67
• Study Type: interventional
• Target: 40
• Locations: 8 countries
• Sites: 39

Brief Summary

The Phase 1 part of the study is conducted to determine the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory solid tumors (excluding central nervous system \[CNS\] tumors). The Phase 2 part of the study is conducted to assess the objective response rate (ORR) and duration of response (DOR) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) and ewing sarcoma (EWS).

Conditions

Refractory or Recurrent Solid Tumors; Rhabdomyosarcoma; Non-Rhabdomyosarcoma Soft Tissue Sarcoma; Ewing Sarcoma

Keywords

eribulin mesilate; irinotecan; combination therapy; children

Outcome Measures

Primary Outcomes (2)

• Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride

  The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities \[DLTs\]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.

  First dose of study drug up to Cycle 1 (Cycle length=21 days)

• Phase 2: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.

  From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 4 months

Secondary Outcomes (13)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From first dose of study drug up to approximately 2 years 4 months

• Number of Participants With Serious Adverse Event (SAE)

  Up to approximately 2 years and 4 months

• Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38

  For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

• Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38

  For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

• Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38

  For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)

Study Arms (1)

Eribulin mesilate plus irinotecan hydrochloride

EXPERIMENTAL

In Schedules A and B, eribulin mesilate at the dose of 1.4 milligrams per meters squared (mg/m\^2) will be administered as an intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle. In Schedule A, irinotecan hydrochloride at the doses of 20 mg/m\^2 or 40 mg/m\^2 will be administered as an IV infusion on Days 1 to 5 of a 21-day cycle. In Schedule B, irinotecan hydrochloride at the doses of 100 mg/m\^2 or 125 mg/m\^2 will be administered as an IV infusion on Days 1 and 8 of a 21-day cycle.

Drug: Eribulin mesilate; Drug: Irinotecan hydrochloride

Interventions

Eribulin mesilate DRUG

IV infusion

Also known as: E7389

Eribulin mesilate plus irinotecan hydrochloride

Irinotecan hydrochloride DRUG

IV infusion

Also known as: (S)-4,11-diethyl-39 3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-4-yl-[1,4'-bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate

Eribulin mesilate plus irinotecan hydrochloride

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Phase 1: Participants must be diagnosed with histologically confirmed solid tumors (excluding CNS tumors), which is relapsed or refractory, and for which there are no currently available therapies.
• Phase 2: Participants must be diagnosed with histologically confirmed RMS, NRSTS or EWS which is relapsed or refractory having received at least 1 prior therapy, including primary treatment.
• Phase 1: Participants must have either measurable or evaluable disease as per RECIST 1.1.
• Phase 2: Participants must have measurable disease as per RECIST 1.1.
• Participant's current disease state must be one for which there is no known curative therapy.
• Participant's performance score must be \>=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 the performance score.
• Participants must have fully recovered from the acute toxic effects of all prior anticancer treatments prior to study drug administration:
• Must not have received myelosuppressive chemotherapy within 21 days prior to study drug administration (42 days if prior nitrosourea).
• Must not have received a long-acting growth factor (example, Neulasta) within 14 days or a short-acting growth factor within 7 days.
• Must not have received an antineoplastic targeted therapy within 14 days.
• Must not have received immunotherapy, example, tumor vaccines, within 42 days.
• Must not have received monoclonal antibodies within at least 3 half-lives of the antibody after its last dose.
• Must not have received radiotherapy (XRT) within 14 days prior to study drug administration (small field) or 42 days for craniospinal XRT, or if \>=50% radiation of pelvis.
• At least 84 days must have elapsed after stem cell infusion prior to study drug administration
• No evidence of active graft-versus-host disease (GVHD) and at least 100 days must have elapsed after allogeneic bone marrow transplant or stem cell infusion prior to study drug administration

You may not qualify if:

• Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 h before the first dose of study drug.
• Females of childbearing potential 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, that is:
• Total abstinence (if it is their preferred and usual lifestyle)
• An intrauterine device (IUD) or intrauterine system (IUS)
• A contraceptive implant
• An oral contraceptive OR
• Do not have a vasectomized partner with confirmed azoospermia.
• Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, 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:
• Participants receiving corticosteroids who have not been on a stable dose for at least 7 days prior to study drug administration.
• Participants who are currently receiving other anticancer agents.
• Participants who are receiving cyclosporine, tacrolimus or other agents to prevent GVHD post bone marrow transplant.
• Participants who are receiving strong cytochrome P450 3A4 (CYP3A4) inhibitors and inducers including traditional herbal medicinal products (example, St. John's Wort).
• Phase 1: Received prior therapy with eribulin mesilate within 6 months prior to study drug administration.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (39)

Hopitaux de La Timone

Marseille, Bouches-du-Rhône, 13385, France

Location

Centre Oscar Lambret

Lille, Nord, 59020, France

Location

Centre Léon Berard

Lyon, Rhône, 69008, France

Location

Eisai Trial Site 4

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Eisai Trial Site 2

Frankfurt am Main, Hesse, 60590, Germany

Location

Eisai Trial Site 5

Göttingen, Lower Saxony, 37075, Germany

Location

Eisai Trial Site 1

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Eisai Trial Site 3

Berlin, 13353, Germany

Location

Eisai Trial Site 6

Essen, 45122, Germany

Location

Aghia Sophia' Children's General Hospital of Athens

Athens, Attica, 115 27, Greece

Location

AHEPA University General Hospital of Thessaloniki

Thessaloniki, 546 36, Greece

Location

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 00165, Italy

Location

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, 00168, Italy

Location

Istituto G Gaslini Ospedale Pediatrico IRCCS

Genoa, Liguria, 16147, Italy

Location

Ospedale Infantile Regina Margherita

Turin, Piedmont, 10126, Italy

Location

Azienda Ospedaliera A Meyer

Florence, Tuscany, 50139, Italy

Location

Azienda Ospedaliera Di Padova

Padua, Veneto, 35128, Italy

Location

Istituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, Masovian Voivodeship, 04-730, Poland

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, Catalonia, 08035, Spain

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Catalonia, 08950, Spain

Location

Hospital Infantil Universitario Niño Jesus

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Kinderspital Zürich - Eleonorenstiftung

Zurich, CH-8032, Switzerland

Location

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Alder Hey Childrens Hospital

Liverpool, Merseyside, L12 2AP, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Royal Marsden Hospital - Surrey

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

The Leeds Teaching Hospitals Charitable Foundation - Leeds Childrens Hospital (LCH)

Leeds, Yorkshire, LS1 3EX, United Kingdom

Location

University College London

London, NW1 2BU, United Kingdom

Location

Royal Manchester Childrens Hospital

Manchester, M13 9WL, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing

Interventions

eribulin; Irinotecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

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

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 10, 2017
• Study Start: March 5, 2018
• Primary Completion: May 17, 2021
• Study Completion: May 17, 2021
• Last Updated: June 28, 2022
• Results First Posted: June 28, 2022

Record last verified: 2021-06

Locations

GR (2); GB (11); ES (6); IT (8); PL (2); FR (3); DE (6); CH (1)