Refractory or Recurrent Solid TumorsPhase 1/2NCT03245450
Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan Hydrochloride in Children With Refractory or Recurrent Solid Tumors
A Phase 1/2 study testing Eribulin mesilate and Irinotecan hydrochloride in people with Refractory or Recurrent Solid Tumors and Rhabdomyosarcoma, run by Eisai Inc. at 39 sites in 8 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months to 25 years
- Conditions the study is for
- Refractory or Recurrent Solid Tumors, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma
- What is being tested?
- Eribulin mesilate and Irinotecan hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 39 sitesin 8 countries
- Study dates
- 5 Mar 2018to 17 May 2021
- Phase
- Phase 1/2
- 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 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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
- Participants must have adequate bone marrow function, defined as:
- Peripheral absolute neutrophil count (ANC) >=1.0*10^9/liter (L).
- Platelet count >=100*10^9/L (not receiving platelet transfusions within a 7-day period prior to study drug administration).
- Hemoglobin (Hb) at least 8.0 grams per deciliter (g/dL) at baseline (blood transfusions are allowed during the screening period to correct Hb values <8.0 g/dL).
- Participants must have adequate renal function, defined as:
- A serum creatinine based on age/gender, derived from the Schwartz formula for estimating glomerular filtration rate (GFR), per protocol-specified criteria.
- Serum creatinine clearance or GFR >=50 milliliters/minute/1.73 m^2, based on a 12 or 24 hours (h) urine creatinine collection.
- Participants must have adequate liver function, defined as:
- Bilirubin (sum of conjugated + unconjugated) <=1.5 times the upper limit of normal (ULN) for age.
- Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*ULN (in the case of liver metastases <=5*ULN), unless there are bone metastases, in which case liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
- Serum albumin >=2 g/dL.
- All participants and/or their parents or guardians must sign a written informed consent.
- Participants must be willing to comply with all aspects of the protocol.
Who cannot join
- 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
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- 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.
- Phase 2: Received prior therapies with eribulin mesilate or irinotecan hydrochloride (for prior irinotecan hydrochloride, participants can be included if there was no tumor progression during irinotecan therapy).
- Any other malignancy that required treatment (except non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ), within 2 years prior to study drug administration.
- Has hypersensitivity to either study drug or any of the excipients.
- Has a known prior history of viral hepatitis (B or C) as demonstrated by positive serology (presence of antigens) or have an uncontrolled infection requiring treatment
- Has >Grade 1 peripheral sensory neuropathy or >Grade 1 peripheral motor neuropathy graded according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies.
- Has cardiac pathology, defined as:
- Participants with known congestive heart failure, symptomatic or Left ventricular (LV) ejection fraction <50% or shortening fraction <27% and participants with congenital long QT syndrome, bradyarrhythmias, or QT interval (QTc)>480 milliseconds on at least 2 separate electrocardiograms (ECGs).
- Has CNS disease: Participants with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy and have discontinued the use of corticosteroids for this indication for at least 28 days prior to study drug administration. Participants must be clinically stable. It is not the intention of this protocol to treat participants with active brain metastases.
- Note: Screening CNS imaging for participants with a known history of CNS disease is required.
- Have had or are planning to have the following invasive procedures:
- Major surgical procedure or significant traumatic injury within 28 days prior to study drug administration.
- Laparoscopic procedure or open biopsy within 7 days prior to study drug administration
- Central line placement or subcutaneous port placement is not considered major surgery.
- Core biopsy, including bone marrow biopsy within 2 days prior to study drug administration.
- Fine needle aspirate within 3 days prior to study drug administration.
- Participants with known human immunodeficiency virus (HIV); due to lack of available safety data for eribulin therapy in HIV infected participants.
- Has any serious concomitant illness that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments (including active or severe chronic inflammatory bowel disease or bowel obstruction).
- Has received a live-virus vaccination within 30 days of planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.
Trial locations and contacts
39 sites in 8 countries.
39 sites in 8 countries
United Kingdom11 sites
Birmingham Children's Hospital
Birmingham, West Midlands, B4 6NH
Addenbrooke's Hospital
Cambridge, Cambridgeshire, CB2 0QQ
The Leeds Teaching Hospitals Charitable Foundation - Leeds Childrens Hospital (LCH)
Leeds, Yorkshire, LS1 3EX
Alder Hey Childrens Hospital
Liverpool, Merseyside, L12 2AP
University College London
London, NW1 2BU
Royal Manchester Childrens Hospital
Manchester, M13 9WL
The Christie NHS Foundation Trust
Manchester, M20 4BX
Royal Victoria Infirmary
Newcastle, NE1 4LP
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Southampton General Hospital
Southampton, Hampshire, SO16 6YD
Royal Marsden Hospital - Surrey
Sutton, Surrey, SM2 5PT
Italy8 sites
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
Bologna, Emilia-Romagna, 40138
Azienda Ospedaliera A Meyer
Florence, Tuscany, 50139
Istituto G Gaslini Ospedale Pediatrico IRCCS
Genoa, Liguria, 16147
Istituto Nazionale Dei Tumori
Milan, 20133
Azienda Ospedaliera Di Padova
Padova, Veneto, 35128
Ospedale Pediatrico Bambino Gesù
Rome, Lazio, 00165
Fondazione Policlinico Universitario A Gemelli
Rome, Lazio, 00168
Ospedale Infantile Regina Margherita
Turin, Piedmont, 10126
Germany6 sites
Eisai Trial Site 1
Aachen, North Rhine-Westphalia, 52074
Eisai Trial Site 3
Berlin, 13353
Eisai Trial Site 6
Essen, 45122
Eisai Trial Site 2
Frankfurt am Main, Hesse, 60590
Eisai Trial Site 4
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Eisai Trial Site 5
Göttingen, Lower Saxony, 37075
Spain6 sites
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, Catalonia, 08035
Hospital Sant Joan de Deu
Esplugues de Llobregat, Catalonia, 08950
Hospital Infantil Universitario Niño Jesus
Madrid, 28009
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
France3 sites
Centre Oscar Lambret
Lille, Nord, 59020
Centre Léon Berard
Lyon, Rhône, 69008
Hopitaux de La Timone
Marseille, Bouches-du-Rhône, 13385
Greece2 sites
Aghia Sophia' Children's General Hospital of Athens
Athens, Attica, 115 27
AHEPA University General Hospital of Thessaloniki
Thessaloniki, 546 36
Poland2 sites
Instytut Pomnik Centrum Zdrowia Dziecka
Warsaw, Masovian Voivodeship, 04-730
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, Lower Silesian Voivodeship, 50-556
About this study
Official title: A Phase 1/2 Single-arm Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan in Children With Refractory or Recurrent Solid Tumors
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
- Being tested
- Eribulin mesilate, Irinotecan hydrochloride
- Keywords
- eribulin mesilate, irinotecan, combination therapy, children
- Medical subject headings
- Rhabdomyosarcoma, Sarcoma, Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eribulin mesilateDrug
Also called E7389
IV infusion
Also called (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
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Eribulin mesilate; Drug: Irinotecan hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Measured: From first dose of study drug up to approximately 2 years 4 months
Number of Participants With Serious Adverse Event (SAE)
SAE was defined as any untoward medical occurrence at any dose 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: Up to approximately 2 years and 4 months
Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
Measured: 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
Measured: 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
Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.
Measured: 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, Total Clearance (CL) of Eribulin and Irinotecan
CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
Measured: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan
Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
Measured: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
Measured: 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, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38
AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
Measured: 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 2: Progression Free Survival (PFS)
PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
Measured: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months
Phase 2: Clinical Benefit Rate (CBR)
CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than [>] 11 weeks). 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 <10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
Measured: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months
Model Predicted Apparent Total Body Clearance (CL) of Eribulin
Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.
Measured: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)
Volume of Distribution Estimates From the Population PK Model for Eribulin
Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.
Measured: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2017
- Study start5 Mar 2018
- Primary completion17 May 2021
- Study completion17 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Refractory or Recurrent Solid TumorsStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03245450
- Sponsor's protocol ID
- E7389-G000-213
- Other IDs
- 2016-003352-67, 2016
- Status last verified
- Jun 2021
- First submitted
- 8 Aug 2017
- Last updated
- 28 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Single-arm Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan in Children With Refractory or Recurrent Solid Tumors
- ClinicalTrials.gov ID
- NCT03245450
- Acronym / sponsor ID
- E7389-G000-213
- Conditions
- Refractory or Recurrent Solid Tumors, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, Ewing Sarcoma
- Keywords
- eribulin mesilate, irinotecan, combination therapy, children
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Mar 2018 (actual)
- Primary completion
- 17 May 2021 (actual)
- Study completion
- 17 May 2021 (actual)
- First posted
- 10 Aug 2017 (actual)
- Results
- Posted 28 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eribulin mesilate plus irinotecan hydrochloride | Experimental | Drug: Eribulin mesilate, Drug: Irinotecan hydrochlorideIn 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. |
Who may qualify
- Ages
- 6 months to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- 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.
Key exclusion criteria (33 listed)
- 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:
- 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:
- Phase 1: Received prior therapy with eribulin mesilate within 6 months prior to study drug administration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eribulin mesilateAlso: E7389IV infusion | Drug | Eribulin mesilate plus irinotecan hydrochloride |
| Irinotecan hydrochlorideAlso: (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, trihydrateIV infusion | Drug | Eribulin mesilate plus irinotecan hydrochloride |
Primary outcome
Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride
Time frame: First dose of study drug up to Cycle 1 (Cycle length=21 days)
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.
Phase 2: Objective Response Rate (ORR)
Time frame: 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
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.
13 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to approximately 2 years 4 months
Number of Participants With Serious Adverse Event (SAE)
Time frame: Up to approximately 2 years and 4 months
Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
Time frame: 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
Time frame: 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
Time frame: 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, Total Clearance (CL) of Eribulin and Irinotecan
Time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan
Time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
Time frame: 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, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38
Time frame: 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 2: Progression Free Survival (PFS)
Time frame: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months
Phase 2: Clinical Benefit Rate (CBR)
Time frame: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months
Model Predicted Apparent Total Body Clearance (CL) of Eribulin
Time frame: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)
Volume of Distribution Estimates From the Population PK Model for Eribulin
Time frame: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
39 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Eribulin mesilate and Irinotecan hydrochloride in people with Refractory or Recurrent Solid Tumors and Rhabdomyosarcoma, run by Eisai Inc. at 39 sites in 8 countries.
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 28 inclusion and 33 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 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United Kingdom, Italy, Germany, Spain, France and 3 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 Jun 2022). 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?
Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride (time frame: First dose of study drug up to Cycle 1 (Cycle length=21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jun 2022.