TERMINATED

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

Conditions

Medulloblastoma, Childhood Medulloblastoma Recurrent Medulloblastoma Sonic Hedgehog (SHH) positive

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2019-07-25

Study Completion:2025-08-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT03904862

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Phase I Skeletally-immature: 1. 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. 2. 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. 3. Patient must be ≥ 3 and ≤ 18 years of age at the time of enrollment. 4. Patients enrolled on the Phase I study must have a BSA as noted below: 2. Phase II Skeletally-mature: 3. Surgical Study: 1. Surgical resection must be clinically indicated. 2. Must be ≥3 years at time of enrollment. 3. Must be amenable to receiving CX-4945 for 5-7 days prior to surgery 4. All Phases: 1. 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. 2. Prior Therapy 3. 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. 4. If neurological deficits are present, must have been stable for a minimum of 1 week prior to enrollment. 5. Must have a Karnofsky/Lansky Performance status ≥50% 6. Must have adequate organ and marrow function 7. Subjects receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment. 8. Female patients of childbearing potential must have a negative pregnancy test. 9. 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. 10. Parent or legal guardian must be able to understand and willing to sign the written informed consent.	1. Nursing mothers due to an unknown but potential risk for adverse events in nursing infants. 2. 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. 3. 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. 4. 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. 5. Corrected QT (QTc) interval is \>480ms 6. Patients who are receiving other anti-cancer or investigational drug therapy 7. Patients who are on warfarin or statins.

Inclusion Criteria

Exclusion Criteria

1. Phase I Skeletally-immature:
1. 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.
2. 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.
3. Patient must be ≥ 3 and ≤ 18 years of age at the time of enrollment.
4. Patients enrolled on the Phase I study must have a BSA as noted below:
2. Phase II Skeletally-mature:
3. Surgical Study:
1. Surgical resection must be clinically indicated.
2. Must be ≥3 years at time of enrollment.
3. Must be amenable to receiving CX-4945 for 5-7 days prior to surgery
4. All Phases:
1. 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.
2. Prior Therapy
3. 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.
4. If neurological deficits are present, must have been stable for a minimum of 1 week prior to enrollment.
5. Must have a Karnofsky/Lansky Performance status ≥50%
6. Must have adequate organ and marrow function
7. Subjects receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.
8. Female patients of childbearing potential must have a negative pregnancy test.
9. 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.
10. Parent or legal guardian must be able to understand and willing to sign the written informed consent.

1. Nursing mothers due to an unknown but potential risk for adverse events in nursing infants.
2. 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.
3. 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.
4. 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.
5. Corrected QT (QTc) interval is \>480ms
6. Patients who are receiving other anti-cancer or investigational drug therapy
7. Patients who are on warfarin or statins.

Contacts and Locations

Principal Investigator

Ralph Salloum, MD

STUDY_CHAIR

Dana-Farber Cancer Institute

Study Locations (Sites)

Children's Hospital of Los Angeles

Los Angeles, California, 90026

United States

Stanford University and Lucile Packard Children's Hospital

Palo Alto, California, 94304

United States

Children's National Medical Center

Washington D.C., District of Columbia, 20010

United States

University of Florida

Gainesville, Florida, 32608

United States

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322

United States

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

Chicago, Illinois, 60611

United States

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

Nationwide Children's Hospital

Columbus, Ohio, 43205

United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15201

United States

St. Jude Children Research Hospital

Memphis, Tennessee, 38105

United States

Baylor College of Medicine

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Pediatric Brain Tumor Consortium

Ralph Salloum, MD, STUDY_CHAIR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-07-25

Study Completion Date2025-08-11

Study Record Updates

Study Start Date2019-07-25

Study Completion Date2025-08-11

Terms related to this study

Keywords Provided by Researchers

Medulloblastoma
Sonic Hedgehog (SHH) positive

Additional Relevant MeSH Terms

Medulloblastoma, Childhood
Medulloblastoma Recurrent
Medulloblastoma