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

NCT03904862 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: PBTC-053UM1CA081457NCI-2019-00180
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 12

Brief 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

Conditions

Medulloblastoma, Childhood; Medulloblastoma Recurrent; Medulloblastoma

Keywords

Medulloblastoma; Sonic Hedgehog (SHH) positive

Outcome Measures

Primary Outcomes (4)

• Phase I: Maximum tolerated dose of CX-4945

  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.

  4 weeks

• Phase I: Plasma pharmacokinetics of CX-4945 in skeletally-immature children

  To report the plasma drug concentration of CX-4945 on this schedule in skeletally-immature children

  4 weeks

• Surgical Study: Intratumoral PK concentrations

  Average tumor CX-4945 concentrations.

  Prior to starting CX-4945 (Day -5 or -7), prior to dose on Day -3, prior to dose on Day -1, day of surgery and during surgery at the time of tissue collection

• Phase II: Sustained objective response rate (PR-CR) rate in the skeletally mature cohort

  Percentage of patients who achieve sustained objective response.

  Up to 2 years from enrollment

Secondary Outcomes (5)

• Progression free survival

  Up to 3 years from enrollment

• Objective response rate in the skeletally-immature cohort

  Up to 2 years from enrollment

• Plasma pharmacokinetics of CX-4945 in skeletally-mature subjects

  4 weeks

• Relative frequency of genomic alterations in archival tissue

  At time of enrollment

• Surgical study: Reduction in CK2-mediated signaling in tumor.

  4 weeks

Study Arms (3)

Phase I - Skeletally-immature

EXPERIMENTAL

Skeletally-immature children with refractory or recurrent medulloblastoma of the SHH group

Drug: CX 4945

Phase II - Skeletally-mature

EXPERIMENTAL

Skeletally-mature subjects with refractory or recurrent medulloblastoma of the SHH group

Drug: CX 4945

Surgical

EXPERIMENTAL

Subjects 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.

Drug: CX 4945

Interventions

CX 4945 DRUG

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

Also known as: Silmitasertib sodium

Phase I - Skeletally-immature; Phase II - Skeletally-mature; Surgical

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Phase II Skeletally-mature:
• a. 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.
• b. 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• Senhwa Biosciences, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• St. Jude Children's Research Hospital: collaborator

Study Sites (12)

Children's Hospital of Los Angeles

Los Angeles, California, 90026, United States

Location

Stanford University and Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15201, United States

Location

St. Jude Children Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Medulloblastoma; Microphthalmia, Isolated, with Coloboma 5

Interventions

silmitasertib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Ralph Salloum, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2019
• First Posted: April 5, 2019
• Study Start: July 25, 2019
• Primary Completion: August 11, 2025
• Study Completion: August 11, 2025
• Last Updated: October 30, 2025

Record last verified: 2025-10

Locations

US (12)