A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma
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.
- 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.
- 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
Name Not Available
Name Not Available
Contact: Marcella West Aguilar
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
Secondary IDs NCI-2017-01329
Clinicaltrials.gov ID NCT02748135