Relapsed or Refractory Medulloblastoma (MB), Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS)Phase 1NCT02748135
A Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma
A Phase 1 study testing TB-403 20mg/kg, TB-403 50mg/kg and TB-403 100mg/kg in people with Relapsed or Refractory Medulloblastoma (MB), Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS), run by Oncurious NV at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Relapsed or Refractory Medulloblastoma (MB), Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS)
- What is being tested?
- TB-403 20mg/kg, TB-403 50mg/kg and TB-403 100mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 10 sitesUnited States
- Study dates
- May 2016to 6 Oct 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Provide written informed consent (Subject or legal representative)
- Be > 6 months and < 18 years of age. For each dose cohort, the first 3 subjects must be at least 2 years of age
- Have a histologically-confirmed diagnosis of MB, NB, ES, or ARMS
- Have documented relapse or refractoriness after standard-of-care therapy
- Have undergone magnetic resonance imaging (MRI) for MB (brain [all cohorts] and spinal cord [cohort 4 only], 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
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- Have adequate organ function, defined as:
- Peripheral absolute neutrophil count ≥ 1.5 × 10^9/L
- Platelet count ≥ 100 × 10^9/L (transfusion to reach this level is permitted)
- 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)
- Creatinine clearance > 50mL/min/1.73m2 or 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
- 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.
Who cannot join
- 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. Subjects must be within the following timelines relative to first dose of study treatment:
- Myelosuppressive chemotherapy: Must not have received within 2 weeks (6 weeks if prior nitrosourea)
- Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Sponsor
- Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g., tumor vaccines
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- Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody
- Radiotherapy: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site
- Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 2 months must have elapsed since transplant
- Have participated in another therapeutic clinical trial with an investigational drug within 1 month before first dose of study treatment
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Study site
Austin, Texas, 78723
Study site
Boston, Massachusetts, 02115
Study site
Charleston, South Carolina, 29425
Study site
Dallas, Texas, 75235
Study site
Grand Rapids, Michigan, 49503
Study site
Hackensack, New Jersey, 07601
Study site
Hartford, Connecticut, 06106
Study site
Little Rock, Arkansas, 72202
Study site
Oakland, California, 94609
Study site
St Louis, Missouri, 63104
About this study
Official title: A Phase 1, Open-Label, Multicenter, Dose Escalation Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma, Neuroblastoma, Ewing Sarcoma or Alveolar Rhabdomyosarcoma
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.
Read the detailed description
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).
- Being tested
- TB-403 20mg/kg, TB-403 50mg/kg, TB-403 100mg/kg, TB-403 175mg/kg
- Medical subject headings
- Recurrence, Medulloblastoma, Neuroblastoma, Sarcoma, Ewing, Rhabdomyosarcoma, Alveolar
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TB-403 20mg/kgDrug
bi-weekly intravenous doses of TB-403 20mg/kg
TB-403 50mg/kgDrug
bi-weekly intravenous doses of TB-403 50mg/kg
TB-403 100mg/kgDrug
bi-weekly intravenous doses of TB-403 100mg/kg
TB-403 175mg/kgDrug
bi-weekly intravenous doses of TB-403 175mg/kg
| Study group | Role | What they receive |
|---|---|---|
| TB-403 20mg/kg | Experimental | Not described Receives: Drug: TB-403 20mg/kg |
| TB-403 50mg/kg | Experimental | Not described Receives: Drug: TB-403 50mg/kg |
| TB-403 100mg/kg | Experimental | Not described Receives: Drug: TB-403 100mg/kg |
| TB-403 175mg/kg | Experimental | Not described Receives: Drug: TB-403 175mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day28
Secondary outcomes (5)
TB-403 total exposure (AUC∞) after single ascending dose
Measured: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 Dose/CL after single ascending dose
Measured: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 Volume of the central compartment (Vc) after single ascending dose
Measured: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 Volume of distribution at steady-state (Vss) after single ascending dose
Measured: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
TB-403 terminal half-life (t½,z) after single ascending dose
Measured: Day 1, day 4, day 8, day 15, day 29, day 60, day 90, day 165 and day 195.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2016 (estimated)
- Study startMay 2016
- Primary completion6 Oct 2020
- Study completion6 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Medulloblastoma (MB), Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncurious NV
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Beat Childhood Cancer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02748135
- Sponsor's protocol ID
- ONC-403-001
- Status last verified
- Jan 2021
- First submitted
- 8 Apr 2016
- Last updated
- 13 Jan 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Multicenter, Dose Escalation Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma, Neuroblastoma, Ewing Sarcoma or Alveolar Rhabdomyosarcoma
- ClinicalTrials.gov ID
- NCT02748135
- Acronym / sponsor ID
- ONC-403-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Oncurious NVIndustry (pharma, biotech, devices)
- Collaborators
- Beat Childhood Cancer
- Study start
- May 2016
- Primary completion
- 6 Oct 2020 (actual)
- Study completion
- 6 Oct 2020 (actual)
- First posted
- 22 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TB-403 20mg/kg | Experimental | Drug: TB-403 20mg/kg |
| TB-403 50mg/kg | Experimental | Drug: TB-403 50mg/kg |
| TB-403 100mg/kg | Experimental | Drug: TB-403 100mg/kg |
| TB-403 175mg/kg | Experimental | Drug: TB-403 175mg/kg |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Provide written informed consent (Subject or legal representative)
- Be > 6 months and < 18 years of age. For each dose cohort, the first 3 subjects must be at least 2 years of age
- Have a histologically-confirmed diagnosis of MB, NB, ES, or ARMS
- Have documented relapse or refractoriness after standard-of-care therapy
- Have undergone magnetic resonance imaging (MRI) for MB (brain [all cohorts] and spinal cord [cohort 4 only], 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
Key exclusion criteria (17 listed)
- 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. Subjects must be within the following timelines relative to first dose of study treatment:
- Have participated in another therapeutic clinical trial with an investigational drug within 1 month before first dose of study treatment
- Have any known active uncontrolled infection
- Have had major surgery or bone fracture within 28 days before first dose of study treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TB-403 20mg/kgbi-weekly intravenous doses of TB-403 20mg/kg | Drug | TB-403 20mg/kg |
| TB-403 50mg/kgbi-weekly intravenous doses of TB-403 50mg/kg | Drug | TB-403 50mg/kg |
| TB-403 100mg/kgbi-weekly intravenous doses of TB-403 100mg/kg | Drug | TB-403 100mg/kg |
| TB-403 175mg/kgbi-weekly intravenous doses of TB-403 175mg/kg | Drug | TB-403 175mg/kg |
Primary outcome
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
5 secondary outcomes
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.
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2021.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TB-403 20mg/kg, TB-403 50mg/kg and TB-403 100mg/kg in people with Relapsed or Refractory Medulloblastoma (MB), Neuroblastoma (NB), Ewing Sarcoma (ES) and Alveolar Rhabdomyosarcoma (ARMS), run by Oncurious NV at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2021.