Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 157 for:    eribulin

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03245450
Recruitment Status : Recruiting
First Posted : August 10, 2017
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

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).


Condition or disease Intervention/treatment Phase
Refractory or Recurrent Solid Tumors Rhabdomyosarcoma Non-Rhabdomyosarcoma Soft Tissue Sarcoma Ewing Sarcoma Drug: Eribulin mesilate Drug: Irinotecan hydrochloride Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 111 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 22, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Eribulin mesilate plus irinotecan hydrochloride
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
IV infusion
Other Name: E7389

Drug: Irinotecan hydrochloride
IV infusion
Other Name: (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




Primary Outcome Measures :
  1. Phase 1: Maximum tolerated dose (MTD) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory solid tumors (excluding CNS). [ Time Frame: Up to 36 months ]
    The MTD is defined as the highest dose level at which less than one-third of participants experience a dose-limiting toxicity (DLT [side effects that prevent a dose increase]) during Cycle 1 of the therapy. Participants less than (<) 12 months of age will not be analyzed for this endpoint.

  2. Phase 1: Recommended phase 2 dose (RP2D) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory solid tumors (excluding CNS). [ Time Frame: Up to 36 months ]
    The RP2D will be based on evaluation of safety, efficacy, and pharmacokinetic data .

  3. Phase 2: Objective response rate (ORR) [ Time Frame: Up to 36 months ]
    ORR is defined as the percentage of participants achieving the best overall response of confirmed partial response (PR) or complete response (CR), as determined by investigator review.


Secondary Outcome Measures :
  1. Phase 1 and Phase 2: Number of participants with any treatment-emergent (TE) serious adverse event (SAE) [ Time Frame: Up to 36 months ]
    An SAE is any untoward medical occurrence that at any dose: results in death; is life threatening (ie, the participant was at immediate risk of death from the adverse event [AE] as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). A TEAE is defined as an AE that emerges during treatment, having been absent at pretreatment (baseline) or (1) reemerges during treatment, having been present at pretreatment (baseline) but stopped before treatment, or (2) worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.

  2. Phase 1 and Phase 2: Number of participants with any TEAE [ Time Frame: Up to 36 months ]
    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with the medicinal product. A TEAE is defined as an AE that emerges during treatment, having been absent at pretreatment (baseline) or (1) reemerges during treatment, having been present at pretreatment (baseline) but stopped before treatment, or (2) worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.

  3. Phase 1: Mean value of maximum observed plasma concentration (Cmax) [ Time Frame: Predose up to multiple timepoints postdose Cycle 1 Day 8; cycle length = 21 days ]
    For participants ≥12 months of age and >10 kg: Cycle 1, Day 1 at the end of the irinotecan infusion (irinotecan is administered first), and at the end of the eribulin infusion, then at 1, 2, 4, 6 and 24, hours post-eribulin infusion. Both irinotecan (and its metabolite) and eribulin will be assayed. At 72 and 120 hours post-eribulin infusion, eribulin only will be assayed. For participants <12 months of age as well as those ≥12 months of age and ≤10 kg (participants <6 kg will not have pharmacokinetic [PK] samples taken): Cycle 1, Day 1 at the end of the irinotecan infusion (irinotecan is administered first) and then immediately after the end of the eribulin infusion (ie 10 ± 5 minutes from the start of the eribulin infusion). Cycle 1, Day 4 or 5: During the collection of the first twice weekly complete blood count (CBC) sample. Cycle 1, Day 8: Immediately after the end of the eribulin infusion (ie 10 ± 5 minutes from the start of the eribulin infusion).

  4. Phase 2: Mean value of Cmax [ Time Frame: Eribulin assay: Cycle 1, Day 1 (at the end of the infusion, 0.5 to 6 hours and 24 to 120 hours after eribulin infusion) and on Cycle 1, Day 8 (pre-dose of eribulin and at the end of the infusion). ]
    Cmax is the highest concentration of drug in the blood that is measured after a dose.

  5. Phase 1: Mean value of time of maximum observed concentration following drug administration (tmax) [ Time Frame: Predose up to multiple timepoints postdose Cycle 1 Day 8; cycle length = 21 days ]
    For participants ≥12 months of age and >10 kg: Cycle 1, Day 1 at the end of the irinotecan infusion (irinotecan is administered first), and at the end of the eribulin infusion, then at 1, 2, 4, 6 and 24, hours post-eribulin infusion. Both irinotecan (and its metabolite) and eribulin will be assayed. At 72 and 120 hours post-eribulin infusion, eribulin only will be assayed. For participants <12 months of age as well as those ≥12 months of age and ≤10 kg (participants <6 kg will not have PK samples taken): Cycle 1, Day 1 at the end of the irinotecan infusion (irinotecan is administered first) and then immediately after the end of the eribulin infusion (ie 10 ± 5 minutes from the start of the eribulin infusion). Cycle 1, Day 4 or 5: During the collection of the first twice weekly CBC sample. Cycle 1, Day 8: Immediately after the end of the eribulin infusion (ie 10 ± 5 minutes from the start of the eribulin infusion).

  6. Phase 2: Mean value of tmax [ Time Frame: Eribulin assay: Cycle 1, Day 1 (at the end of the infusion, 0.5 to 6 hours and 24 to 120 hours after eribulin infusion) and on Cycle 1, Day 8 (pre-dose of eribulin and at the end of the infusion) ]
    Tmax is the time to the highest concentration of drug in the blood that is measured after a dose.

  7. Phase 1: Mean value of area under the concentration-time curve (AUC) [ Time Frame: Predose up to multiple timepoints postdose Cycle 1 Day 8; cycle length = 21 days ]
    For participants ≥12 months of age and >10 kg: Cycle 1, Day 1 at the end of the irinotecan infusion (irinotecan is administered first), and at the end of the eribulin infusion, then at 1, 2, 4, 6 and 24, hours post-eribulin infusion. Both irinotecan (and its metabolite) and eribulin will be assayed. At 72 and 120 hours post-eribulin infusion, eribulin only will be assayed. For participants <12 months of age as well as those ≥12 months of age and ≤10 kg (participants <6 kg will not have PK samples taken): Cycle 1, Day 1 at the end of the irinotecan infusion (irinotecan is administered first) and then immediately after the end of the eribulin infusion (ie 10 ± 5 minutes from the start of the eribulin infusion). Cycle 1, Day 4 or 5: During the collection of the first twice weekly CBC sample. Cycle 1, Day 8: Immediately after the end of the eribulin infusion (ie 10 ± 5 minutes from the start of the eribulin infusion).

  8. Phase 2: Mean value of AUC [ Time Frame: Eribulin assay: Cycle 1, Day 1 (at the end of the infusion, 0.5 to 6 hours and 24 to 120 hours after eribulin infusion) and on Cycle 1, Day 8 (pre-dose of eribulin and at the end of the infusion) ]
    AUC represents the overall amount of drug in the bloodstream after dosing.

  9. Phase 2: Progression-free survival (PFS) [ Time Frame: Up to 36 months ]
    PFS is defined as the time from the first dose date to the date of disease progression as determined by investigator review, or death.

  10. Phase 2: The Clinical Benefit Rate (CBR) at week 12 [ Time Frame: Week 12 ]
    CBR is defined as the percentage of participants with a best overall response (BOR) of CR, PR or durable stable disease (SD) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (durable SD >11 weeks).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Participants must be

  • Greater than or equal to (≥)12 months to less than (<)18 years old at the time of consent.
  • Greater than (>) 6 months and <12 months at the time of consent (Phase 1 and Schedule A only) participants will be enrolled one dose level behind the dose level at which the ≥12 months to <18 years old group are enrolled.

Inclusion Criteria:

  • 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 rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) or ewing sarcoma (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 less than or equal to (≤)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 (eg, 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, eg, 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 less than 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 radioisotope 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.

Exclusion Criteria:

  • 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, 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 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 (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:

    • 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 CYP3A4 inhibitors and inducers including traditional herbal medicinal products (eg 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.
  • Any 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 greater than 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 (ECG).
  • 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.
  • 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 but must be placed at least 2 days prior to study drug administration.
    • 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 patients.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03245450


Contacts
Layout table for location contacts
Contact: Eisai Medical Information 1-888-274-2378 esi_oncmedinfo@eisai.com

Locations
Layout table for location information
France
Centre Oscar Lambret Recruiting
Lille, France
Centre Léon Berard Recruiting
Lyon, France
Hopitaux de La Timone Not yet recruiting
Marseille, France
Germany
Uniklinik RWTH Aachen Kinderklinik Recruiting
Aachen, Germany
Charite Virchow Kinderklinik - CC17 Recruiting
Berlin, Germany
Uniklinik Essen AoR Kinderklinik Recruiting
Essen, Germany
Klinik fur Kinder und Jugendmed - KKJM Recruiting
Frankfurt, Germany
Uniklinik Freiburg Kindermedizin Klinik IV Recruiting
Freiburg, Germany
Uniklinik Gottingen Kindermedizin Recruiting
Gottingen, Germany
Kinderklinik Muenchen Schwabing Not yet recruiting
Muenchen, Germany
Greece
Aghia Sophia' Children's General Hospital of Athens Recruiting
Athens, Greece
Italy
Azienda Ospedaliera A Meyer Recruiting
Firenze, Italy
Istituto Nazionale Dei Tumori Recruiting
Milan, Italy
Ospedale Pediatrico Bambino Gesù Recruiting
Roma, Italy
Spain
Hospital Universitario Vall d'Hebron - PPDS Recruiting
Barcelona, Spain
Hospital Sant Joan de Deu Not yet recruiting
Esplugues De Llobregat, Spain
Hospital Infantil Universitario Niño Jesus Recruiting
Madrid, Spain
Hospital Universitario La Paz Recruiting
Madrid, Spain
Hospital Universitario Virgen del Rocio Recruiting
Sevilla, Spain
Hospital Universitari i Politecnic La Fe de Valencia Recruiting
Valencia, Spain
United Kingdom
The University of Birmingham Not yet recruiting
Birmingham, United Kingdom
Bristol Royal Hospital For Children Not yet recruiting
Bristol, United Kingdom
Addenbrooke's Hospital Not yet recruiting
Cambridge, United Kingdom
The Leeds Teaching Hospitals Charitable Foundation - Leeds Childrens Hospital (LCH) Not yet recruiting
Leeds, United Kingdom
Alder Hey Childrens Hospital Not yet recruiting
Liverpool, United Kingdom
University College London Not yet recruiting
London, United Kingdom
Christie Hospital Not yet recruiting
Manchester, United Kingdom
Royal Manchester Childrens Hospital Not yet recruiting
Manchester, United Kingdom
Royal Victoria Infirmary Not yet recruiting
Newcastle, United Kingdom
John Radcliffe Hospital Not yet recruiting
Oxford, United Kingdom
Southampton General Hospital Not yet recruiting
Southampton, United Kingdom
Royal Marsden Hospital - Surrey Not yet recruiting
Surrey, United Kingdom
Sponsors and Collaborators
Eisai Inc.

Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03245450     History of Changes
Other Study ID Numbers: E7389-G000-213
2016-003352-67 ( EudraCT Number )
First Posted: August 10, 2017    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: June 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:
eribulin mesilate
irinotecan
combination therapy
children

Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Myosarcoma
Neoplasms, Muscle Tissue
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents