A Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma

January 11, 2021 updated by: Oncurious NV

A Phase 1, Open-Label, Multicenter, Dose Escalation Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma, Neuroblastoma, Ewing Sarcoma or Alveolar Rhabdomyosarcoma

The purpose of this study is to assess the safety and tolerability profile of TB-403 (humanized monoclonal antibody against placental growth factor (PlGF)) in pediatric subjects with relapsed or refractory Medulloblastoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The maximum tolerated dose of TB-403 will be determined in pediatric subjects with relapsed or refractory Medulloblastoma (MB) and as well Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS).

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
    • California
      • Oakland, California, United States, 94609
    • Connecticut
      • Hartford, Connecticut, United States, 06106
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
    • Missouri
      • Saint Louis, Missouri, United States, 63104
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
    • South Carolina
      • Charleston, South Carolina, United States, 29425
    • Texas
      • Austin, Texas, United States, 78723
      • Dallas, Texas, United States, 75235

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provide written informed consent (Subject or legal representative)
  2. Be > 6 months and < 18 years of age. For each dose cohort, the first 3 subjects must be at least 2 years of age
  3. Have a histologically-confirmed diagnosis of MB, NB, ES, or ARMS
  4. Have documented relapse or refractoriness after standard-of-care therapy
  5. Have undergone magnetic resonance imaging (MRI) for MB (brain [all cohorts] and spinal cord [cohort 4 only], a computerized tomography (CT) / metaiodobenzylguanidine (MIBG) scan for NB, and CT / magnetic resonance imaging (MRI) for ES or ARMS within 1 month prior to first dose of study treatment
  6. Have a Lansky score ≥ 40 for subjects up to 16 years of age or a Karnofsky score ≥ 40 for subjects 16 years of age to < 18 years

  7. Have adequate organ function, defined as:

    • Peripheral absolute neutrophil count ≥ 1.5 × 10^9/L
    • Platelet count ≥ 100 × 10^9/L (transfusion to reach this level is permitted)
    • Hemoglobin ≥ 8mg/dL (transfusion to reach this level is permitted)
    • International normalized ratio (INR) < 1.5; partial thromboplastin time (PTT) < 1.5 upper limit of normal (ULN)
    • Creatinine clearance > 50mL/min/1.73m2 or serum creatinine ≤ specified maximum values based on age, as described below:
    • 6 months to 3 years of age: serum creatinine ≤ 0.4mg/dL
    • 3 to 13 years of age: serum creatinine ≤ 0.7mg/dL
    • > 13 years of age: serum creatinine ≤ 1mg/dL
    • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 2.5 × ULN; serum bilirubin < 1.5 × ULN
  8. Have no symptoms of cranial hypertension or convulsions within 14 days before Cycle 1 Day 1 (anti-epileptic drugs and corticoids are allowed to control any preexisting symptoms)
  9. If female of child bearing potential, must not be lactating and must have a negative pregnancy test (blood or urine, at the discretion of the investigator) prior to enrollment and use effective contraception during study participation. Women should continue effective contraception for 3 months following last dose of TB-403.
  10. If a sexually-active male, must agree to use a latex condom during any sexual contact with females of child bearing potential while participating in the study and for 3 months following last dose of TB-403.
  11. For subjects on corticosteroids for endocrine deficiencies or tumor-associated symptoms, must be on a stable (or decreasing) dose for at least 7 days before first dose of study treatment.

Exclusion Criteria:

  1. Have any clinically significant disease considered by the investigator to interfere with study participation

  2. Have not fully recovered from the acute toxic effects of prior anticancer therapy (e.g., chemotherapy, immunotherapy, radiation therapy) or are currently receiving cytotoxic chemotherapy, immunotherapy or radiation therapy. Subjects must be within the following timelines relative to first dose of study treatment:

    • Myelosuppressive chemotherapy: Must not have received within 2 weeks (6 weeks if prior nitrosourea)
    • Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor
    • Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Sponsor
    • Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g., tumor vaccines
    • Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody
    • Radiotherapy: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site
    • Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 2 months must have elapsed since transplant
  3. Have participated in another therapeutic clinical trial with an investigational drug within 1 month before first dose of study treatment
  4. Have any known active uncontrolled infection
  5. Have had major surgery or bone fracture within 28 days before first dose of study treatment
  6. Have previously received TB-403
  7. Have a history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
  8. Are receiving increasing doses of corticosteroids
  9. Are eligible for a curative treatment option
  10. Have had a prior thrombotic event (e.g., pulmonary embolism, deep vein thrombosis) or are currently receiving therapeutic or prophylactic doses of anticoagulants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TB-403 20mg/kg
Drug: TB-403 20mg/kg
bi-weekly intravenous doses of TB-403 20mg/kg
Experimental: TB-403 50mg/kg
Drug: TB-403 50mg/kg
bi-weekly intravenous doses of TB-403 50mg/kg
Experimental: TB-403 100mg/kg
Drug: TB-403 100mg/kg
bi-weekly intravenous doses of TB-403 100mg/kg
Experimental: TB-403 175mg/kg
Drug: TB-403 175mg/kg
bi-weekly intravenous doses of TB-403 175mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary safety endpoint will be the determination of the maximum tolerated dose (MTD) / study maximum dose (SMD) based on the occurrence of dose-limiting toxicities (DLTs) during the 28-day DLT assessment period.
Time Frame: Day28
Day28

Secondary Outcome Measures

Outcome Measure
Time Frame
TB-403 total exposure (AUC∞) after single ascending dose
Time Frame: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 Dose/CL after single ascending dose
Time Frame: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 Volume of the central compartment (Vc) after single ascending dose
Time Frame: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 Volume of distribution at steady-state (Vss) after single ascending dose
Time Frame: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 terminal half-life (t½,z) after single ascending dose
Time Frame: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oncurious NV

Collaborators

Beat Childhood Cancer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Actual)

October 6, 2020

Study Completion (Actual)

October 6, 2020

Study Registration Dates

First Submitted

April 8, 2016

First Submitted That Met QC Criteria

April 19, 2016

First Posted (Estimate)

April 22, 2016

Study Record Updates

Last Update Posted (Actual)

January 13, 2021

Last Update Submitted That Met QC Criteria

January 11, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONC-403-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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