Clinical Trial - NCT02748135

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

Recruiting

Sponsor: Oncurious NV

Collaborators: BioInvent International AB, Beat Childhood Cancer

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02748135

Protocol Info

Short Description: TB-403 Pediatrics w/ Medulloblastoma/Neuroblastoma/EwingSarcoma/AlveolarRhabdomyosarcoma
Long Description: A Two-Part Study of TB-403 in Pediatric Subjects with Relapsed or Refractory Medulloblastoma, Neuroblastoma, Ewing Sarcoma, or Alveolar Rhabdomyosarcoma
MGH Status: Open
Sponsor: Oncurious NV
Disease Program: Pediatrics

Next Steps


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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.
Condition Title Intervention Phase
Relapsed or Refractory Medulloblastoma (MB) (Part A: Also Include Neuroblastoma (NB), Ewing Sarcoma TB-403 20mg/kg TB-403 50mg/kg TB-403 100mg/kg TB-403 175mg/kg Phase 1/Phase 2
Study Type Interventional
Official Title A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma

Primary Outcome Measures

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] [Designated as safety issue: ]


Secondary Outcome Measures

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.] [Designated as safety issue: ]

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.] [Designated as safety issue: ]

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.] [Designated as safety issue: ]

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.] [Designated as safety issue: ]

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.] [Designated as safety issue: ]

Estimated Enrollment: 36
Study Start Date: May 2016
Estimated Study Completion Date: March 2023
Estimated Primary Completion Date: June 2022
Arms Assigned Interventions

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

Experimental:TB-403 x mg/kg

In part B of the study, subjects will receive the maximum tolerated dose as determined in part A.

Eligibility

Ages Eligible for Study: 18 Years-18 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02748135

Locations

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

Sponsors and Collaborators

Oncurious NV

BioInvent International AB

Beat Childhood Cancer

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02748135
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Neuroblastoma

Rhabdomyosarcoma

Sarcoma, Ewing

Medulloblastoma

Rhabdomyosarcoma, Alveolar

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 16, 2019