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Medulloblastoma, ChildhoodPhase 1/2NCT03904862

Testing the Safety and Tolerability of CX-4945 in Patients With Recurrent Medulloblastoma Who May or May Not Have Surgery

A Phase 1/2 study testing CX 4945 in people with Medulloblastoma, Childhood and Medulloblastoma Recurrent, run by Pediatric Brain Tumor Consortium at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a multi center, Phase I, Phase II and surgical study of the CX-4945 drug (silmitasertib sodium) for patients with recurrent SHH (Sonic Hedgehog) medulloblastoma Read more about this study

Who is it for?
Ages 3 years and older
What is being tested?
CX 4945
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
12 sitesUnited States
Study dates
25 Jul 2019to 11 Aug 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Phase I Skeletally-immature:
  • Patient must be skeletally-immature at the time of study enrollment, defined as females with a bone age < 14 years and males with a bone age < 16 years.
  • Patients who participate in the expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions (Section 12.2.2). Patients with measurable extraneural disease only are also eligible.
  • Patient must be ≥ 3 and ≤ 18 years of age at the time of enrollment.
  • Patients enrolled on the Phase I study must have a BSA as noted below:
  • Dose Level 0 (400 mg/m2 BID): Minimum - 0.84m2; Maximum - 2.25m2 Dose Level 1 (600 mg/m2 BID): Minimum - 0.60m2; Maximum - 2.00m2 Dose Level 2 (800 mg/m2 BID): Minimum - 0.63m2; Maximum - 2.00m2
Show all 40Show fewer
  • Phase II Skeletally-mature:
  • Patients must be skeletally-mature, defined as females with a bone age ≥14 years and males with a bone age ≥ 16 years OR have a chronological age >18 years.
  • Patients must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions. Patients with measurable extraneural disease only are also eligible.
  • Surgical Study:
  • Surgical resection must be clinically indicated.
  • Must be ≥3 years at time of enrollment.
  • Must be amenable to receiving CX-4945 for 5-7 days prior to surgery
  • All Phases:
  • Patient must have a diagnosis of SHH medulloblastoma that is recurrent or progressive, confirmed histologically and by CLIA-certified methylation-based subgroup testing at Cincinnati Children's Hospital Medical Center (CCHMC), Memorial Sloan Kettering Cancer Center (MSKCC), National Cancer Institute (NCI), or Nationwide Children's Hospital (NCH). Results from prior testing at these designated sites using the same approaches described for this study will be accepted.
  • Prior Therapy
  • Must have received prior therapy which included radiation therapy and recovered from acute treatment related toxicities.
  • Must have received the last dose of myelosuppressive therapy at least 21 days prior to enrollment and at least 42 days if nitrosourea.
  • Must have received the last dose of another investigational or biologic agent ≥7 days prior. For agents known to have adverse events occurring beyond 7 days, the period must be extended to accommodate the longer interval. For monoclonal antibodies with prolonged half-lives, at least 3 half-lives must have elapsed.
  • Must have received last fraction of craniospinal or total body irradiation or radiation to ≥50% of the pelvis >12 weeks prior to enrollment. Last fraction of focal irradiation must be >4 weeks prior to enrollment.
  • Must be ≥ 24 weeks since allogeneic stem cell transplant with no evidence of acute graft vs. host disease.
  • Must be ≥12 weeks since autologous stem cell transplant.
  • Must be off all colony-forming growth factors at least 1 week prior to enrollment. Must be off 2 weeks if the subject received a long-acting formulation.
  • If neurological deficits are present, must have been stable for a minimum of 1 week prior to enrollment.
  • Patients with seizure disorders may be enrolled if seizures are well controlled.
  • Must have a Karnofsky/Lansky Performance status ≥50%
  • Must have adequate organ and marrow function
  • Subjects receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.
  • Female patients of childbearing potential must have a negative pregnancy test.
  • Patients of child-bearing or child fathering potential must be willing to use medically acceptable form of birth control while treated on this study and for 3 months after drug cessation.
  • Parent or legal guardian must be able to understand and willing to sign the written informed consent.
  • Exclusion Criteria:
  • 1. All Phases
  • Nursing mothers due to an unknown but potential risk for adverse events in nursing infants.
  • Patients with a history of any other malignancy with the exception of patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment.
  • Patients with any of the following gastrointestinal disorders - difficulty swallowing or active malabsorption, uncontrolled diarrhea, gastritis, ulcerative colitis, Crohn's disease or hemorrhagic coloproctitis, history of gastric or small bowel surgery involving any extent of gastric or small bowel resection.
  • Patients with any clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate therapy, put them at additional risk for toxicity or interfere with the study procedures or results.
  • Corrected QT (QTc) interval is >480ms
  • Patients who are receiving other anti-cancer or investigational drug therapy
  • Patients who are on warfarin or statins.

Who cannot join

None listed.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Florida

    Gainesville, Florida, 32608

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90026

  • St. Jude Children Research Hospital

    Memphis, Tennessee, 38105

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Stanford University and Lucile Packard Children's Hospital

    Palo Alto, California, 94304

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15201

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: PBTC-053: A Pediatric Brain Tumor Consortium Phase I/ II and Surgical Study of CX-4945 in Patients With Recurrent SHH Medulloblastoma

This is a multi center, Phase I, Phase II and surgical study of the CX-4945 drug (silmitasertib sodium) for patients with recurrent SHH (Sonic Hedgehog) medulloblastoma

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) and recommend a Phase II dose of CX-4945 administered orally daily to skeletally-immature children with recurrent SHH (sonic hedgehog) medulloblastoma (Phase I) II. To describe the toxicity profile and define the dose-limiting toxicities associated with CX-4945 in children with recurrent SHH (Sonic hedgehog) medulloblastoma (Phase I) III. To characterize the pharmacokinetics of CX-4945 administered on this schedule in skeletally-immature children with recurrent SHH medulloblastoma (Phase I) IV. To characterize the concentrations of CX-4945 in tumor after administration of CX-4945 and surgical resection (Surgical Study). V. To establish the safety and characterize the toxicity of 1000mg BID continuous dosing of CX-4945 in skeletally-mature patients with recurrent SHH medulloblastoma (Phase II). VI. To estimate the objective response rate associated with CX-4945 in skeletally-mature patients with recurrent SHH medulloblastoma

SECONDARY OBJECTIVES:

  1. To document preliminary antitumor activity of CX-4945 in skeletally-immature children with recurrent SHH medulloblastoma (Phase I). II. To perform a genomic analysis within the confines of a Phase I study to investigate correlation between response to treatment and the presence of specific genomic alterations. and/or specific subgroups of disease (Phase I). III. To explore the ability of CX-4945 at the MTD/ RP2D to inhibit CK2-mediated signaling in tumor (Surgical Study). IV. To characterize the pharmacokinetics of CX-4945 in skeletally-mature patients with recurrent SHH medulloblastoma (Phase II). V. To perform a genomic analysis within the confines of a Phase II study to investigate correlation between response to treatment and the presence of specific genomic alterations and/or specific subgroups of disease (Phase II).

OUTLINE: Phase I component is a dose-escalation study. The Phase II component is to establish the safety of 1000mg BID given continuously.

The study will open with a safety cohort of 3 subjects who are considered skeletally-mature. The initial 3 subjects will be administered CX-4945 twice a day at the adult RP2D of 1000 mg BID or at its BSA adjusted equivalent; however, the dose will be given continuously. If there are not excessive toxicities in this cohort, the study will proceed following the Phase II design for subjects who are skeletally-mature.

Following the safety lead in, the Phase 1 component of this trial will be initiated. Skeletally-immature children with refractory or recurrent medulloblastoma of the SHH subgroup, will be administered CX-4945 twice a day on a continuous basis at a starting dose of 600mg/m2 BID which corresponds approximately to the BSA adjusted recommended Phase 2 dose (RP2D) of 1000mg. The Phase 1 study will escalate doses to determine the maximum tolerated dose skeletally-immature children.

The surgical study will be initiated after the first 3 patients in the skeletally-mature cohort are treated for initial assessment of safety and did not experience excessive toxicity. Skeletally-mature subjects with recurrent or refractory SHH medulloblastoma will be eligible as soon the surgical study is initiated and will receive drug at 1000mg BID or its BSA adjusted equivalent depending upon age and BSA. Skeletally-immature subjects will only be eligible to enroll on the surgical trial once the MTD is defined in the Phase 1 component and will receive drug at the established MTD for this cohort.

After completion of study treatment, patients are followed up to 2 years.

Being tested
CX 4945
Keywords
Medulloblastoma, Sonic Hedgehog (SHH) positive
Medical subject headings
Medulloblastoma, Microphthalmia, Isolated, with Coloboma 5

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CX 4945Drug

    Also called Silmitasertib sodium

    CX-4945 is supplied as 200 mg capsules delivered orally as a formulated API

Study groups in NCT03904862
Study groupRoleWhat they receive
Phase I - Skeletally-immatureExperimentalSkeletally-immature children with refractory or recurrent medulloblastoma of the SHH group
Receives: Drug: CX 4945
Phase II - Skeletally-matureExperimentalSkeletally-mature subjects with refractory or recurrent medulloblastoma of the SHH group
Receives: Drug: CX 4945
SurgicalExperimentalSubjects who are eligible for the Phase I or Phase II arm of the trial and are candidates for surgery, may be enrolled in the surgical arm prior to initiation of the Phase I or Phase II treatment.
Receives: Drug: CX 4945

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

    DLT is any event occurring during the dose-finding period (Course 1) that is at least possibly related to CX-4945, regardless of expectedness. DLTs include: (1) any CX-4945-related AE leading to dose reduction, permanent treatment discontinuation, or treatment delay >14 days (dose modifications per Sections 7.1 and 7.2); (2) non-hematologic toxicity: any Grade 4 event; any Grade 3 event except controllable Grade 3 nausea/vomiting, supportive care-responsive Grade 3 diarrhea, reversible Grade 3 AST/ALT returning to eligibility levels within 7 days of treatment interruption without recurrence on rechallenge, Grade 3 fever, Grade 3 infection, or enteral supplementation-responsive Grade 3 electrolyte abnormalities; and any non-hematologic toxicity persisting ≥14 days that is medically significant or intolerable enough to require treatment interruption; (3) hematologic toxicity: Grade 3/4 thrombocytopenia or Grade 4 neutropenia.

    Measured: up to 4 weeks for each dosing cohort

  2. Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of CX-4945 in Skeletally Immature Patients

    The rolling-6 design was used to estimate the MTD in the Phase I group. The MTD was defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic.

    Measured: 4 weeks

  3. Intratumoral PK Concentrations in Surgical Cohort Participants

    Average tumor CX-4945 concentrations in surgical patients

    Measured: During surgery at the time of tissue collection

  4. Sustained Objective Response (PR-CR) Rate in Skeletally-mature Patients

    A sustained objective responder is defined as a patient who achieves a confirmed partial response or complete response, which also must be sustained for at least 8 weeks with central radiographic confirmation. Response rates will be calculated as the percent of evaluable patients who are responders. Tumor response criteria are determined by changes in size, measured as the longest tumor dimension and its perpendicular. FLAIR, T2 or post contrast T1 weighted images may be used - whichever gives the best estimate of tumor size.

    Measured: Up to 2 years from enrollment

  5. Pharmacokinetic (PK) Parameters of CX4945, Area Under the Curve (AUC), in Skeletally Immature Patients

    The mean of the AUC evaluated at day 1 and day 28 of course 1 in skeletally immature patients who had plasma sample available.

    Measured: Day 1 and day 28 of the course 1.

Secondary outcomes (5)
  1. Progression Free-Survival (PFS)

    The Kaplan-Meier method will be used to estimate the median survival time of PFS. The PFS is defined as the time between treatment initiation until progression or death for any reason for patients who experience an event and last follow-up for patients who are event-free at the time of analysis.

    Measured: up to 24 months from enrollment

  2. Sustained Objective Response (PR-CR) Rate in Skeletally-immature Patients

    A sustained objective responder is defined as a patient who achieves a confirmed partial response or complete response, which also must be sustained for at least 8 weeks with central radiographic confirmation. Response rates will be calculated as the percent of evaluable patients who are responders. Tumor response criteria are determined by changes in size, measured as the longest tumor dimension and its perpendicular. FLAIR, T2 or post contrast T1 weighted images may be used - whichever gives the best estimate of tumor size.

    Measured: Up to 2 years from enrollment

  3. Pharmacokinetic (PK) Parameters of CX4945, Area Under the Curve (AUC), in Skeletally Mature Patients

    The mean of the AUC evaluated on day 1 and day 28 of course 1 in skeletally mature patients with a plasma sample available.

    Measured: Day 1 and day 28 of the course 1.

  4. Correlation Between Response to Treatment and the Presence of Specific Genomic Alterations

    Estimated correlation coefficient between antitumor response and presence of genomic alterations.

    Measured: At time of enrollment

  5. Reduction in CK2-mediated Signaling in Tumor for Surgical Participants

    Change in CK2 activity in tumor tissue from patients on the surgical are at baseline and after treatment.

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2019
  2. Study start25 Jul 2019
  3. Primary completion11 Aug 2025
  4. Study completion11 Aug 2025

Why it stopped: The decision to permanently close PBTC-053 was made following communication from the NCI that the PBTC grant will not be extended beyond March 31, 2026.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03904862
Sponsor's protocol ID
PBTC-053
Other IDs
UM1CA081457, NCI-2019-00180, PBTC-053, PBTC-053
Status last verified
Sep 2026
First submitted
1 Apr 2019
Last updated
19 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CX 4945 in people with Medulloblastoma, Childhood and Medulloblastoma Recurrent, run by Pediatric Brain Tumor Consortium at 12 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 40 inclusion and 0 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: stopped early, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: up to 4 weeks for each dosing cohort). The study lists 5 primary outcomes in all. 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 19 Oct 2026.

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