CNS MalignanciesEarly Phase 1JACOBNCT07017816
A Phase 0/1 Study of cDNA for TP53, Checkpoint Inhibition and Radiation in Children With Recurrent, Progressive or Refractory CNS Malignancies.
A Early Phase 1 study testing SGT-53, hypofractionated radiotherapy with immunotherapy and Nivolumab in people with CNS Malignancies and Medulloblastoma Recurrent, run by Children's National Research Institute at 1 site in United States.
Trial summary
This clinical trial is studying a drug called SGT-53 along with radiation and another drug called Nivolumab. It's for children with brain tumors that have come back, gotten worse, or didn't get better with earlier treatments. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- CNS Malignancies, Medulloblastoma Recurrent, ATRT Recurrent
- What is being tested?
- SGT-53, hypofractionated radiotherapy with immunotherapy and Nivolumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2025to 1 May 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Tumor
- Patients must have a recurrent, progressive, or refractory CNS malignancy for which there are not known curative options.
- Medulloblastoma, ATRT, High grade gliomas, pineoblastomas, embryonal tumors NOS, CNS sarcomas, ependymomas, other high-grade malignancies that failed first line therapies.
- Patients should have received radiation for standard up-front therapy. iii. Patients must have received at least one line of standard of care treatment without limitation to the number of treatments received. b. Evidence of clinical and/or radiological progressive disease as defined by RAPNO criteria.
- Patients with metastatic disease are eligible d. Patients must have available archival (formalin-fixed paraffin embedded) or fresh tumor tissue for correlative studies.
- Patient Characteristics a. The first 3 patients will be >7 years old to <22 years old i. Following initial successful treatment of the first 3 patients: Patients must be ≥3yrs and <22 years of age.
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- Must have recovered from all surgical interventions prior to the start of the radiation and maintenance phases c. Patients must have a BSA of 0.6m2 or more to be enrolled. 3. Previous treatment
- Patients must have recovered from the acute effects of prior therapy. Adverse events resulting from prior surgical intervention will not be an ineligibility criterion.
- Chemotherapy: Patients must have received their last dose of known chemotherapy at least two (2) weeks prior to receipt of SGT-53.
- Biologic therapy: Patients must have received their last dose of biological agent >7 days prior to receipt of SGT-53.
- Radiation therapy: Patients must be deemed to be a reasonable candidate for hypofractionated irradiation from a clinical standard of care perspective.
- At least 3 months from craniospinal radiation therapy, ii. Other substantial bone marrow irradiation ≥6 weeks prior to enrollment, iii. Local palliative XRT (small volume) ≥2 weeks. iv. if progressive disease is documented by radiological evidence of disease in areas not previously radiated, no minimum time required.
- Corticosteroids: Patients who are receiving dexamethasone or other corticosteroids must be on a stable or decreasing dose for at least one (1) week prior to enrollment. There will be a maximum allowable steroid dose of 0.5mg/m2/day dexamethasone equivalents f. Growth factors: Patients must have received their last dose of any short acting growth factor at least one week prior to treatment, for long acting or pegylated growth factors, the last dose must be at least two (2) weeks prior to start of treatment.
- 4. Neurologic Status
- Patients should be at their neurological baseline for a minimum of one week prior to enrollment.
- 5. Performance Status
- Performance status (KarnofskyPS for >16yrs, or Lansky PS for <16yrs) assessed within two weeks must be >50.
- Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for assessing the performance score.
- 6. Organ Function - Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count >750/ul
- Platelets ≥75,000/ul
- Hemoglobin ≥8g/dL (may be supported with transfusion)
- Total bilirubin ≤1.5x ULN
- ALT/AST ≤3x ULN
- Serum albumin ≥2g/dL
- Normal cardiac function defined as ejection fraction within normal limits for age and gender
- a serum creatinine based on age/gender as below or a creatinine clearance or serum GFR ≥ 70ml/min/1.73m2: Serum Creatinine for age/sex Age Maximum Serum Creatinine (mg/dL) Male Female
- <2 years 0.6 0.6
- <6 years 0.8 0.8
- 6-<10 years 1 1 10-<13 years 1.2 1.2 13- <16 years 1.5 1.4 > 16 years 1.7 1.4 The threshold creatinine values in this table were adapted from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds 106:.522, 1985) utilizing child length and stature data published by the CDC.
- 7. Pregnancy prevention- all patients of childbearing or child fathering potential must be willing to use an acceptable form of birth control while being treated on this study and at least 5 months after receiving the last study treatment.
- 8. Pregnancy status: Female patients must not be pregnant or nursing. Female patients of reproductive potential must also have a negative serum pregnancy test at the time of enrollment.
- 9. Informed Consent - Patient and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Who cannot join
- 1. Low-grade-glioma, craniopharyngioma, and other non-malignant CNS tumors are excluded.
- 2. Patients with diagnosis of diffuse midline gliomas (DMGs) are excluded. 3. Patients with any clinically significant unrelated systemic illness (serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that is likely to interfere with ability to tolerate study therapy or study procedure results.
- 4. Patients with pre-existing cardiac dysfunction defined as baseline EF of less than 35% 5. Patients with pre-existing pulmonary fibrosis, interstitial lung disease, and clinically significant pulmonary lung disease.
- 6. Patients who are receiving any other investigational drug therapy 7. Patients who in the opinion of the investigator cannot adhere to protocol requirements 8. Patients with history of autoimmune diseases that required treatment in the last 2 years are not eligible. Asymptomatic laboratory abnormalities (e.g. ANA, rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder. Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy) is not considered a form of systemic treatment.
- 9. Patients who have received a live vaccine within 30 days of start of study treatment are not eligible.
- 10. Patients with known HIV/AIDS or acute/chronic Hepatitis B or C are excluded.
- 11. Patients who are prohibited from receiving radiation therapy (reached maximum lifetime dose) are not eligible.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's National Hospital
Washington D.C., District of Columbia, 20010
Eugene Hwang, MD
Adriana Fonseca, MD
About this study
Official title: JACOB: Joint Administration of cDNA for TP53, checkpOint Inhibition and Boost/Hypofractionated Radiation. A Phase 0/1 Study in Children With Recurrent, Progressive or Refractory CNS Malignancies.
This clinical trial is studying a drug called SGT-53 along with radiation and another drug called Nivolumab. It's for children with brain tumors that have come back, gotten worse, or didn't get better with earlier treatments. The main questions it aims to answer are:
What is the right dose of SGT-53 that children can safely receive when it is used with radiation and Nivolumab? This dose will be used in the second phase of the trial.
Read more
What side effects are there of SGT-53 when it is used with radiation and Nivolumab?
How does SGT-53 move through the body when given with radiation and Nivolumab?
How much of the SGT-53 drug is found in the tumor tissue? This will be tested in a small group of patients?
Participants will:
For the first treatment cycle:
Get SGT-53 twice per week Get Nivolumab every 2 weeks Receive radiation therapy during week 2
For Cycles 2-6:
Get SGT-53 once per week during even cycles and twice per week during odd cycles Get Nivolumab every 2 weeks For Cycles 7+ Get both SGT-53 and Nivolumab every 2 weeks In the phase 0 part of the study, 4 participants will have genetic testing performed on their tumor tissue after receiving SGT-53. These samples will be compared to another sample taken from the skin.
- Conditions
- CNS Malignancies, Medulloblastoma Recurrent, ATRT Recurrent, Pineoblastoma, Embryonal Neoplasm, Ependymoma Recurrent
- Being tested
- SGT-53, hypofractionated radiotherapy with immunotherapy, Nivolumab
- Medical subject headings
- Central Nervous System Neoplasms, Pinealoma, Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGT-53Drug
SGT-53 is a novel cationic liposome encapsulating a normal human wild type TP53 cDNA sequence in a plasmid backbone. The liposome is decorated on its surface with an anti- transferrin receptor (TfR) single chain antibody fragment (scFv) that is designed to target cancer cells through the binding of the TfRscFv to the transferrin receptor. This complex has been shown to efficiently and specifically deliver the TP53 complementary DNA (cDNA) to the tumor cells via receptor-mediated endocytosis of the cationic liposomal complex. Introduction of the TP53 cDNA sequence restores wild-type p53 (wtp53) function in the apoptotic pathway.
hypofractionated radiotherapy with immunotherapyRadiation
Re-irradiation has rapidly grown into a primary consideration in the context of recurrent pediatric CNS malignancies. While not thought to be curative by itself, it has often resulted in temporary symptomatic improvement as well as occasional radiographic regression or stabilization, although as with any irradiation, may also cause some adverse events.
NivolumabDrug
Given the poor prognosis for children with recurrent CNS malignancies and the importance of p53 function in these tumors, we propose a pilot study of SGT-53 in combination with re-irradiation and checkpoint inhibition followed by maintenance therapy with SGT-53 in combination with nivolumab to evaluate the safety, feasibility and preliminary efficacy. SGT-53 will be added to a salvage regimen utilized in patients with recurrent tumors of re- irradiation and nivolumab followed by combination therapy with SGT-53 and nivolumab.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Patients with recurrent, progressive, or refractory CNS malignancies receiving SGT-53, Nivolumab, and radiation. Receives: Drug: SGT-53; Radiation: hypofractionated radiotherapy with immunotherapy; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and type of toxicity deemed at least probably related to SGT-53
Measured: From enrollment to 3 years from end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2025
- Study start16 Dec 2025
- Primary completion1 May 2028 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CNS MalignanciesStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eugene Hwang, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07017816
- Sponsor's protocol ID
- STUDY00001415
- Acronym
- JACOB
- Status last verified
- Apr 2026
- First submitted
- 4 Jun 2025
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- JACOB: Joint Administration of cDNA for TP53, checkpOint Inhibition and Boost/Hypofractionated Radiation. A Phase 0/1 Study in Children With Recurrent, Progressive or Refractory CNS Malignancies.
- ClinicalTrials.gov ID
- NCT07017816
- Acronym / sponsor ID
- JACOB / STUDY00001415
- Conditions
- CNS Malignancies, Medulloblastoma Recurrent, ATRT Recurrent, Pineoblastoma, Embryonal Neoplasm, Ependymoma Recurrent
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Study start
- 16 Dec 2025 (actual)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 12 Jun 2025 (actual)
- 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.
This clinical trial is studying a drug called SGT-53 along with radiation and another drug called Nivolumab. It's for children with brain tumors that have come back, gotten worse, or didn't get better with earlier treatments. The main questions it aims to answer are:
What is the right dose of SGT-53 that children can safely receive when it is used with radiation and Nivolumab? This dose will be used in the second phase of the trial.
What side effects are there of SGT-53 when it is used with radiation and Nivolumab?
How does SGT-53 move through the body when given with radiation and Nivolumab?
How much of the SGT-53 drug is found in the tumor tissue? This will be tested in a small group of patients?
Participants will:
For the first treatment cycle:
Get SGT-53 twice per week Get Nivolumab every 2 weeks Receive radiation therapy during week 2
For Cycles 2-6:
Get SGT-53 once per week during even cycles and twice per week during odd cycles Get Nivolumab every 2 weeks For Cycles 7+ Get both SGT-53 and Nivolumab every 2 weeks In the phase 0 part of the study, 4 participants will have genetic testing performed on their tumor tissue after receiving SGT-53. These samples will be compared to another sample taken from the skin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: SGT-53, Radiation: hypofractionated radiotherapy with immunotherapy, Drug: NivolumabPatients with recurrent, progressive, or refractory CNS malignancies receiving SGT-53, Nivolumab, and radiation. |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (33 listed)
- Tumor
- Patients should have received radiation for standard up-front therapy. iii. Patients must have received at least one line of standard of care treatment without limitation to the number of treatments received. b. Evidence of clinical and/or radiological progressive disease as defined by RAPNO criteria.
- Patients with metastatic disease are eligible d. Patients must have available archival (formalin-fixed paraffin embedded) or fresh tumor tissue for correlative studies.
- Patient Characteristics a. The first 3 patients will be >7 years old to <22 years old i. Following initial successful treatment of the first 3 patients: Patients must be ≥3yrs and <22 years of age.
- 4. Neurologic Status
Key exclusion criteria (7 listed)
- 1. Low-grade-glioma, craniopharyngioma, and other non-malignant CNS tumors are excluded.
- 2. Patients with diagnosis of diffuse midline gliomas (DMGs) are excluded. 3. Patients with any clinically significant unrelated systemic illness (serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that is likely to interfere with ability to tolerate study therapy or study procedure results.
- 4. Patients with pre-existing cardiac dysfunction defined as baseline EF of less than 35% 5. Patients with pre-existing pulmonary fibrosis, interstitial lung disease, and clinically significant pulmonary lung disease.
- 6. Patients who are receiving any other investigational drug therapy 7. Patients who in the opinion of the investigator cannot adhere to protocol requirements 8. Patients with history of autoimmune diseases that required treatment in the last 2 years are not eligible. Asymptomatic laboratory abnormalities (e.g. ANA, rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder. Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy) is not considered a form of systemic treatment.
- 9. Patients who have received a live vaccine within 30 days of start of study treatment are not eligible.
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 |
|---|---|---|
| SGT-53SGT-53 is a novel cationic liposome encapsulating a normal human wild type TP53 cDNA sequence in a plasmid backbone. The liposome is decorated on its surface with an anti- transferrin receptor (TfR) single chain antibody fragment (scFv) that is designed to target cancer cells through the binding of the TfRscFv to the transferrin receptor. This complex has been shown to efficiently and specifically deliver the TP53 complementary DNA (cDNA) to the tumor cells via receptor-mediated endocytosis of the cationic liposomal complex. Introduction of the TP53 cDNA sequence restores wild-type p53 (wtp53) function in the apoptotic pathway. | Drug | Treatment Arm |
| hypofractionated radiotherapy with immunotherapyRe-irradiation has rapidly grown into a primary consideration in the context of recurrent pediatric CNS malignancies. While not thought to be curative by itself, it has often resulted in temporary symptomatic improvement as well as occasional radiographic regression or stabilization, although as with any irradiation, may also cause some adverse events. | Radiation | Treatment Arm |
| NivolumabGiven the poor prognosis for children with recurrent CNS malignancies and the importance of p53 function in these tumors, we propose a pilot study of SGT-53 in combination with re-irradiation and checkpoint inhibition followed by maintenance therapy with SGT-53 in combination with nivolumab to evaluate the safety, feasibility and preliminary efficacy. SGT-53 will be added to a salvage regimen utilized in patients with recurrent tumors of re- irradiation and nivolumab followed by combination therapy with SGT-53 and nivolumab. | Drug | Treatment Arm |
Primary outcome
Frequency and type of toxicity deemed at least probably related to SGT-53
Time frame: From enrollment to 3 years from end of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing SGT-53, hypofractionated radiotherapy with immunotherapy and Nivolumab in people with CNS Malignancies and Medulloblastoma Recurrent, run by Children's National Research Institute at 1 site 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 33 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julia Batarseh (202-476-5578, jamore@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and type of toxicity deemed at least probably related to SGT-53 (time frame: From enrollment to 3 years from end of treatment.). 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 29 Apr 2026.