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

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ClinicalTrials.gov Identifier: NCT02748135
Recruitment Status : Recruiting
First Posted : April 22, 2016
Last Update Posted : August 15, 2018
Sponsor:
Collaborators:
BioInvent International AB
Beat Childhood Cancer
Information provided by (Responsible Party):
Oncurious NV

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Medulloblastoma (MB) (Part A: Also Include Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS)) Drug: TB-403 20mg/kg Drug: TB-403 50mg/kg Drug: TB-403 100mg/kg Drug: TB-403 ≤175mg/kg Phase 1 Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma
Study Start Date : May 2016
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020


Arm Intervention/treatment
Experimental: TB-403 20mg/kg Drug: TB-403 20mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 20mg/kg

Experimental: TB-403 50mg/kg Drug: TB-403 50mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 50mg/kg

Experimental: TB-403 100mg/kg Drug: TB-403 100mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 100mg/kg

Experimental: TB-403 ≤175mg/kg Drug: TB-403 ≤175mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 ≤175mg/kg

Experimental: TB-403 x mg/kg
In part B of the study, subjects will receive the maximum tolerated dose as determined in part A.
Drug: TB-403 20mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 20mg/kg

Drug: TB-403 50mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 50mg/kg

Drug: TB-403 100mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 100mg/kg

Drug: TB-403 ≤175mg/kg
Up to 12 bi-weekly intravenous doses of TB-403 ≤175mg/kg




Primary Outcome Measures :
  1. In Part A, 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 ]

Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]


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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provide written informed consent (Subject or legal representative)
  2. Be > 6 months and < 18 years of age
  3. Have a histologically-confirmed diagnosis of MB, NB, ES, or ARMS
  4. 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
  5. 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
  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
    • 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
  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. A minimum period of 4 weeks / 28 days is required between the end of prior anticancer therapy and the initiation of TB-403.
  3. 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
  4. Have participated in another therapeutic clinical trial with an investigational drug within 1 month
  5. Have any known active uncontrolled infection
  6. Have had major surgery or bone fracture within 28 days before first dose of study treatment
  7. Have previously received TB-403
  8. Have a history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
  9. Are receiving increasing doses of corticosteroids
  10. Are eligible for a curative treatment option.
  11. Have had a prior thrombotic event (e.g., pulmonary embolism, deep vein thrombosis) or are currently receiving therapeutic or prophylactic doses of anticoagulants.

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): NCT02748135


Contacts
Contact: Study Director, Global Clinical Development +32 16 751 310 info@oncurious.com

Locations
United States, Arkansas
Recruiting
Little Rock, Arkansas, United States, 72202
United States, California
Recruiting
Oakland, California, United States, 94609
United States, Connecticut
Recruiting
Hartford, Connecticut, United States, 06106
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02115
United States, Michigan
Recruiting
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Recruiting
Saint Louis, Missouri, United States, 63104
United States, New Jersey
Recruiting
Hackensack, New Jersey, United States, 07601
United States, South Carolina
Recruiting
Charleston, South Carolina, United States, 29425
United States, Texas
Recruiting
Austin, Texas, United States, 78723
Recruiting
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Oncurious NV
BioInvent International AB
Beat Childhood Cancer

Additional Information:
Responsible Party: Oncurious NV
ClinicalTrials.gov Identifier: NCT02748135     History of Changes
Other Study ID Numbers: ONC-403-001
First Posted: April 22, 2016    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018

Additional relevant MeSH terms:
Neuroblastoma
Rhabdomyosarcoma
Sarcoma, Ewing
Medulloblastoma
Rhabdomyosarcoma, Alveolar
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Glioma