Eribulinmesilat

Author: Julia Dobke, erstellt am: 2017/11/29, Last modification: 2018/03/21

Eribulinmesilat 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
Disease Phase 1: To determine the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) of eribulin mesilate in combination with weekly and daily irinotecan hydrochloride in pediatric subjects with relapsed/refractory extra-cranial solid tumors Phase 2: To assess the objective response rate (ORR) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric subjects with relapsed/refractory rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS)
Type Phase 1/2 trial
Problem / Objectives

Phase 1 (open)

Phase 1 will determine the maximal tolerated dose (MTD) and the recommanded Phase 2 dose (RP2D) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric subjects with relapsed/refractory extra-cranial solid tumors.

Phase 2 (still closed, 02/2018)

Will evaluate the safety and efficacy (objective Response rate) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric subjects with relapsed/refractory RMS and NRSTS, using the combination dose and schedule determined in Phase 1.

Therapy / Study arms

Phase 1:
Phase 1: Will determine the MTD/RP2D of eribulin mesilate in combination with irinotecan hydrochloride in pediatric subjects with relapsed/refractory extra-cranial solid tumors.
Eribulin mesilate will be administered as an intravenous (IV) infusion on Days 1 and 8 of each 21 day cycle, at the RP2D determined in the single-agent dose finding study E7389-A001-113 (1.4 mg/m2).
Irinotecan hydrochloride will be administered as an IV infusion using 2 different dose schedules:
- Days 1-5 of a 21 day cycle at the following doses; 20 mg/m2 and 40 mg/m2
And
-Days 1 and 8 of a 21 day cycle at the following doses; 100 mg/m2 and 125 mg/m2

Pre-study Phase:
Day -14 to -1, computerized tomography (CT) / magnetic resonance imaging (MRI) scans must be performed within 14 days prior to study drug administration. All clinical and laboratory test results to determine eligibility must be performed within 7 days prior to study drug administration, unless otherwise indicated.
Treatment Phase:
The Treatment Phase will start on Day 1 (D1) of Cycle 1 (C1). Subjects will receive eribulin mesilate by IV infusion on Days 1 and 8 of a 21-day cycle together with IV irinotecan hydrochloride administered on either:
-Days 1-5
-Days 1 and 8 of a 21-day cycle (See Study Design of Phase 1).
The most appropriate schedule will be taken forward to Phase 2 and will represent the RP2D (See Study Design of Phase 2).
Subjects in both Phase 1 and Phase 2 will remain on treatment if they are receiving clinical benefit, as outlined in the Duration of Treatment.

Inclusion Criteria
  • Age: ≥12 months to <18 years old at the time of consent.
  • Diagnosis: Phase 1: Histologically confirmed extra-cranial solid tumor, which is relapsed or refractory, and for which there are no currently available therapies. Phase 2: Histologically confirmed RMS or NRSTS which is relapsed or refractory having received at least 1 prior systemic therapy, including primary treatment.
  • Disease status: Phase 1: Subjects must have either measurable or evaluable disease as per RECIST 1.1. Phase 2: Subjects must have measurable disease as per RECIST 1.1.
  • Measurable disease is defined as meeting the following criteria: a. At least 1 lesion of ≥1.0 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 RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). b. 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: Subject’s current disease state must be one for which there is no known curative therapy..
  • Performance level: Performance score ≥50% Karnofsky (for subjects >16 years of age) or Lansky (for subjects ≤16 years of age)
  • Subjects must have fully recovered from the acute toxic effects of all prior anticancer Treatments prior to study drug administration:
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate liver function
  • Informed consent: All subjects and/or their parents or guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Subjects must be willing to comply with all aspects of the protocol.
Exclusion Criteria
  • Females who are breastfeeding or pregnant at Screening or Baseline
  • 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
  • Concomitant Medications: Corticosteroids: Subjects receiving corticosteroids who have not been on a stable dose for at least 7 days prior to study drug administration. Anticancer agents: Subjects who are currently receiving other anticancer agents. Anti-GVHD agents post-transplant: Subjects who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant.
  • Participant 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
  • Participant has > Grade 1 peripheral sensory neuropathy or > Grade 1 peripheral motor neuropathy
  • Participant has cardiac pathology
  • Participant has CNS disease: Subjects 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
  • 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.
  • HIV Infection
  • Participant has any serious concomitant illness that in the opinion of the investigator(s) could affect the subject’s safety or interfere with the study assessments.
Recruitment Up zu 36 participants in Phase 1 und 50 participants in Phase 2
Status Start: 08/2017-expected end: 12/2020
EudraCT 2016-003352-67
Entry Study Register ClinicalTrials.gov: NCThttps://clinicaltrials.gov/ct2/show/NCT03245450
Contact

Principal Investigator

Prof. Dr. Udo Kontny Klinik für Kinder- und Jugendmedizin Universitätsklinikum Aachen Sektion Pädiatrische Onkologie und Stammzelltransplantation Pauwelsstraße 30 52074 Aachen Telefon +49 (241) 80 88892/89902 Fax +49 (241) 80 82481 ukontny@ukaachen.de

Participants Universitätskinderklinik Aachen, Universitätskinderklinik Göttingen, Universitätskinderklinik Freiburg, Universitätskinderklinik Berlin-Charité, Universitätskinderklinik Essen, Universitätskinderklinik Frankfurt
Weitere Informationen Sponsor: Eisai