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

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • Provide written informed consent (Subject or legal representative)
  • Be > 6 months and < 18 years of age
  • Have a histologically-confirmed diagnosis of MB, NB, ES, or ARMS
  • Have documented relapse or refractoriness after at least 1 line (MB and ARMS subjects) or 2 lines (NB and ES subjects) of standard-of-care therapy, including each of the following:
  • Surgery, unless documented contraindication
  • Radiotherapy, unless documented contraindication
  • Chemotherapy, unless documented contraindication
  • Have undergone magnetic resonance imaging (MRI) for MB, 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
  • 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
  • Have adequate organ function, defined as:
  • Peripheral absolute neutrophil count ≥ 1.5 × 10^9/L
  • Platelet count ≥ 100 × 10^9/L
  • 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); d-dimer < 250ng/mL
  • 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
  • Creatinine clearance > 50mL/min
  • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 2.5 × ULN; serum bilirubin < 1.5 × ULN
  • 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)
  • 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.
  • 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.
  • 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

  • Have any clinically significant disease considered by the investigator to interfere with study participation
  • 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. A minimum period of 4 weeks / 28 days is required between the end of prior anticancer therapy and the initiation of TB-403.
  • Have had cancer other than MB, NB, ES or RMS for Part A of the study or cancer other than MB in the previous 5 years for Parts A and B
  • Have participated in another therapeutic clinical trial with an investigational drug within 1 month
  • Have any known active uncontrolled infection
  • Have had major surgery or bone fracture within 28 days before first dose of study treatment
  • Have previously received TB-403
  • Have a history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
  • Are receiving increasing doses of corticosteroids
  • Are eligible for a curative treatment option.
  • Have had a prior thrombotic event (e.g., pulmonary embolism, deep vein thrombosis) or are currently receiving therapeutic or prophylactic doses of anticoagulants.

Locations & Contacts

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

South Carolina

Charleston
Medical University of South Carolina
Status: Active
Name Not Available

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Marcella West Aguilar
Phone: 214-648-1479
Email: marcella.aguilar@utsouthwestern.edu

Trial Objectives and Outline

The study will be conducted in 2 parts. In part A, 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). In part B of the clinical trial, the safety and tolerability of TB-403 at the maximum tolerated dose will be evaluated in pediatric subjects with relapsed or refractory Medulloblastoma.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Oncurious NV

Trial IDs

Primary ID ONC-403-001
Secondary IDs NCI-2017-01329
Clinicaltrials.gov ID NCT02748135