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

Study ID
STU 052016-012

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Caitlyn Ambrose
2144562162
Caitlyn.Ambrose@childrens.com

Principal Investigator
Theodore Laetsch, M.D.

Official Title

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

Brief Overview

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.

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.

Eligibility

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.