Clinical Trials /

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

NCT02748135

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.

Related Conditions:
  • Alveolar Rhabdomyosarcoma
  • Ewing Sarcoma
  • Medulloblastoma
  • Neuroblastoma
Recruiting Status:

Suspended

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma
  • Official Title: A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma

Clinical Trial IDs

  • ORG STUDY ID: ONC-403-001
  • NCT ID: NCT02748135

Conditions

  • Relapsed or Refractory Medulloblastoma (MB) (Part A: Also Include Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS))

Interventions

DrugSynonymsArms
TB-403 20mg/kgTB-403 20mg/kg
TB-403 50mg/kgTB-403 50mg/kg
TB-403 100mg/kgTB-403 100mg/kg
TB-403 ≤175mg/kgTB-403 ≤175mg/kg

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
TB-403 20mg/kgExperimental
  • TB-403 20mg/kg
TB-403 50mg/kgExperimental
  • TB-403 50mg/kg
TB-403 100mg/kgExperimental
  • TB-403 100mg/kg
TB-403 ≤175mg/kgExperimental
  • TB-403 ≤175mg/kg
TB-403 x mg/kgExperimentalIn part B of the study, subjects will receive the maximum tolerated dose as determined in part A.
  • TB-403 20mg/kg
  • TB-403 50mg/kg
  • TB-403 100mg/kg
  • TB-403 ≤175mg/kg

Eligibility 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.
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:TB-403 total exposure (AUC∞) after single ascending dose
Time Frame:Day 1, day 4, day 8, day 14, day 28, day 56, day 112, day 168 and day 308.
Safety Issue:
Description:
Measure:TB-403 Dose/CL after single ascending dose
Time Frame:Day 1, day 4, day 8, day 14, day 28, day 56, day 112, day 168 and day 308.
Safety Issue:
Description:
Measure:TB-403 Volume of the central compartment (Vc) after single ascending dose
Time Frame:Day 1, day 4, day 8, day 14, day 28, day 56, day 112, day 168 and day 308.
Safety Issue:
Description:
Measure:TB-403 Volume of distribution at steady-state (Vss) after single ascending dose
Time Frame:Day 1, day 4, day 8, day 14, day 28, day 56, day 112, day 168 and day 308.
Safety Issue:
Description:
Measure:TB-403 terminal half-life (t½,z) after single ascending dose
Time Frame:Day 1, day 4, day 8, day 14, day 28, day 56, day 112, day 168 and day 308.
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oncurious NV

Last Updated

February 21, 2017