A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR

NCT02687386 | Terminated Phase 1 DMC

• 1 other identifier: KCA001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours.

Conditions

Solid Tumours; CNS Tumours

Keywords

Recurrent; Refractory

Outcome Measures

Primary Outcomes (3)

• MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0

  To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR

  Day 28 (cycle 1)

• Incidence of treatment-related adverse events as assessed by CTCAE v4.0

  To define and describe the toxicities of EEDVSMit administered on these schedules in children with recurrent/refractory solid or CNS tumours

  Up to 35 days after the completion of study treatment

• Incidence of all adverse events as assessed by CTCAE v4.0, clinically significant changes in vital signs, ECGs and clinical laboratory tests

  Assess the safety and tolerability of EEDVSMit in children with recurrent/refractory solid or CNS tumours.

  Up to 35 days after the completion of study treatment

Secondary Outcomes (3)

• Assess disease response according to RECIST version 1.1 for children with recurrent/refractory solid or CNS tumours

  Up to 35 days after the completion of study treatment

• Assess overall survival

  12 months from the date the last subject was enrolled in the study.

• Time to response assessed by radiological imaging and RECIST v1.1

  Evaluated at Day 56 (after cycle 2), then every second cycle to the end of study treatment (up to 12 months)

Study Arms (1)

Mitoxantrone packaged EDV

EXPERIMENTAL

Mitoxantrone packaged EDV (EnGeneIC Dream Vector)

Drug: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)

Interventions

Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle) DRUG

EnGeneIC Delivery Vehicles (EDVs) are nanocells which can be loaded with anti-cancer drugs (mitoxantrone in this study) and targeted to tumor cells. These bacterially-derived nanocells are coated in bispecific antibodies (BsAb) that recognize oncogenic receptors on the tumor cell surface. Once bound to the tumour cell, the targeted and drug-loaded EDVs are endocytosed and release their toxic payload to destroy the tumor cell.

Also known as: EDV also stands for EnGeneIC Dream Vector

Mitoxantrone packaged EDV

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be ≥ 2 years and ≤ 21 years old at the time of study enrolment.
• Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
• Patients must have relapsed or refractory solid or CNS tumours or have a diagnosis of DIPG. Patients must have had histologic verification of malignancy at original diagnosis or relapse, or a diagnosis of DIPG by MRI imaging.
• Patients must have either measurable or evaluable disease for Part B of the study only
• Patient'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.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study.
• Any active uncontrolled infection
• Patients who are known to be serologically positive for Hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis.
• Known positive test for human immunodeficiency virus infection
• Patients with disease of any major organ system that would compromise their ability to withstand therapy
• Concurrent or prior (within 7 days of enrolment) anticoagulation therapy, except low molecular weight heparins or low dose aspirin
• Patients receiving corticosteroids must be on a stable dose that has not been increased for at least 7 days prior to study enrolment.
• Patients who are currently receiving another investigational drug are ineligible.
• Patients who are currently receiving other antineoplastic agents are ineligible.
• All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the Study Chair.
• Patient will not be available for protocol-required study visits or procedures, to the best of the subject/parent/guardian's and investigator's knowledge.
• Patient has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject/parent/guardian to give written informed consent and/or to comply with all required study procedures.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• Patients will be screened for antibodies to S. typhimurium and will not be eligible until antibodies are non-detectable
• Patients will be screened for IL6 and TNFa cytokines and will not be eligible until levels are less than 3x times the detectable limit of the assay.

Sponsors & Collaborators

• Dr David Ziegler: lead
• Engeneic Pty Limited: collaborator

Study Sites (2)

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Location

Related Publications (1)

• Evans L, Walker R, MacDiarmid J, Brahmbhatt H, Anazodo A, McCowage G, Gifford AJ, Kavallaris M, Trahair T, Ziegler DS. A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor. Target Oncol. 2024 May;19(3):333-342. doi: 10.1007/s11523-024-01051-2. Epub 2024 Mar 28.

  PMID: 38546944 DERIVED

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David Ziegler, MBBS

  Sydney Children's Hospitals Network

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 22, 2016
• Study Start: February 8, 2016
• Primary Completion: December 29, 2021
• Study Completion: December 29, 2021
• Last Updated: February 14, 2022

Record last verified: 2022-01

Locations

AU (2)