RECRUITING

Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma

Conditions

Medulloblastoma Medulloblastoma, Childhood Medulloblastoma Recurrent Ependymoma Ependymoma Malignant Ependymoma of Brain Individualized Treatment Plan Genetic Screening Screening

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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

The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility in the pilot phase of performing real-time drug screening on tissue taken during surgery in patients with relapsed medulloblastoma or ependymoma and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with relapsed medulloblastoma and ependymoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.

Official Title

A Pilot Feasibility and Efficacy (Phase 2) Trial of Real Time Drug Screening and Genomic Testing to Determine an Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma

Quick Facts

Study Start:2022-02-22

Study Completion:2028-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05057702

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:12 Months to 39 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible. 2. Participants must have surgically accessible disease. 3. Prior Therapy: 1. The participant must have received at least one prior therapy at the time of initial diagnosis. 2. Relapsed medulloblastoma or relapsed ependymoma are eligible. 3. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines * Participants must have received last chemotherapy or biologic agent at least 7 days prior to registration. * Monoclonal antibody treatment: \> 21 days prior to registration. * Bevacizumab participants must have received last dose \> 21 days prior to study registration 4. Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study. 5. Radiation - Participants must have: 1. Had their last fraction of local irradiation to primary tumor \>= 12 weeks prior to registration. 2. Had their last fraction of craniospinal irradiation or total body irradiation \>= 12 weeks prior to registration 3. At least 14 days after local palliative radiation (small-port) 6. Age \>=12 months to \<= 39 years of age. 7. Karnofsky \>= 50 for participants \> 16 years of age and Lansky \>= 50 for participants \<= 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 8. Corticosteroids: Participants who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration. 9. Organ Function Requirements (within 7 days prior to study registration) 1. Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) \>= 750/mm\^3 * Platelet count \>= 75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment). * Hemoglobin \>= 8 g/dl. 2. Adequate Renal Function Defined as: * Creatinine clearance or radioisotope GFR \>= 70 milliliter/minute (mL/min) /1.73 m\^2 or * A serum creatinine based on age/sex as follows: * 1 to \< 2 years / 0.6 / 0.6. * 2 to \< 6 years / 0.8 / 0.8. * 6 to \< 10 years / 1 / 1. * 10 to \< 13 years / 1.2 / 1.2. * 13 to \< 16 years / 1.5 / 1.4. * \>= 16 years / 1.7 / 1.4. * - The threshold creatinine values in this table were derived from the Schwartz formula for estimating Glomerular filtration rate (GFR) utilizing child length and stature data published by the Center for Disease Control (CDC) (Schwartz GJ and Gauthier B 1985). 3. Adequate Liver Function Defined as: * Total Bilirubin \<= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \< 3 x ULN or direct bilirubin \< 1.5 x ULN. * Alanine aminotransferase (ALT) \<= 3x ULN. * Aspartate aminotransferase (AST) \<= 3x ULN. 10. The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect pregnancy while participating in this study, the treating physician should be informed immediately. 11. Adequate neurologic function defined as participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug. 12. Participants must enroll on the Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies (PNOC COMP) study if PNOC COMP is open to accrual at the enrolling institution 13. A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.	1. Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 2. Participants who are receiving any other investigational agents. 3. Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs. 4. Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection. 6. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy. 7. Participants must not receive any tumor-directed therapy after enrollment, except for surgical resection/ biopsy.

Inclusion Criteria

Exclusion Criteria

1. Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible.
2. Participants must have surgically accessible disease.
3. Prior Therapy:
1. The participant must have received at least one prior therapy at the time of initial diagnosis.
2. Relapsed medulloblastoma or relapsed ependymoma are eligible.
3. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines
* Participants must have received last chemotherapy or biologic agent at least 7 days prior to registration.
* Monoclonal antibody treatment: \> 21 days prior to registration.
* Bevacizumab participants must have received last dose \> 21 days prior to study registration
4. Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study.
5. Radiation - Participants must have:
1. Had their last fraction of local irradiation to primary tumor \>= 12 weeks prior to registration.
2. Had their last fraction of craniospinal irradiation or total body irradiation \>= 12 weeks prior to registration
3. At least 14 days after local palliative radiation (small-port)
6. Age \>=12 months to \<= 39 years of age.
7. Karnofsky \>= 50 for participants \> 16 years of age and Lansky \>= 50 for participants \<= 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
8. Corticosteroids: Participants who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration.
9. Organ Function Requirements (within 7 days prior to study registration)
1. Adequate Bone Marrow Function Defined as:
* Peripheral absolute neutrophil count (ANC) \>= 750/mm\^3
* Platelet count \>= 75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
* Hemoglobin \>= 8 g/dl.
2. Adequate Renal Function Defined as:
* Creatinine clearance or radioisotope GFR \>= 70 milliliter/minute (mL/min) /1.73 m\^2 or
* A serum creatinine based on age/sex as follows:
* 1 to \< 2 years / 0.6 / 0.6.
* 2 to \< 6 years / 0.8 / 0.8.
* 6 to \< 10 years / 1 / 1.
* 10 to \< 13 years / 1.2 / 1.2.
* 13 to \< 16 years / 1.5 / 1.4.
* \>= 16 years / 1.7 / 1.4.
* - The threshold creatinine values in this table were derived from the Schwartz formula for estimating Glomerular filtration rate (GFR) utilizing child length and stature data published by the Center for Disease Control (CDC) (Schwartz GJ and Gauthier B 1985).
3. Adequate Liver Function Defined as:
* Total Bilirubin \<= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \< 3 x ULN or direct bilirubin \< 1.5 x ULN.
* Alanine aminotransferase (ALT) \<= 3x ULN.
* Aspartate aminotransferase (AST) \<= 3x ULN.
10. The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect pregnancy while participating in this study, the treating physician should be informed immediately.
11. Adequate neurologic function defined as participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.
12. Participants must enroll on the Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies (PNOC COMP) study if PNOC COMP is open to accrual at the enrolling institution
13. A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

1. Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
2. Participants who are receiving any other investigational agents.
3. Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
4. Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
6. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.
7. Participants must not receive any tumor-directed therapy after enrollment, except for surgical resection/ biopsy.

Contacts and Locations

Study Contact

PNOC Operation Office

CONTACT

415-502-1600

PNOC027@ucsf.edu

Principal Investigator

Sabine Mueller, MD, PhD, MAS

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Robert Wechsler-Reya, PhD

STUDY_CHAIR

Columbia University

Margaret Shatara, MD

STUDY_CHAIR

Washington University School of Medicine

Megan Paul, MD

STUDY_CHAIR

Rady Children's Hospital

Lindsay Kilburn, MD

STUDY_CHAIR

Children's National Research Institute

Study Locations (Sites)

Children's Hospital of Los Angeles

Los Angeles, California, 90027

United States

Rady Children's Hospital

San Diego, California, 92123

United States

University of California, San Francisco

San Francisco, California, 94143

United States

Children's National Hospital

Washington, District of Columbia, 20010

United States

St. Louis Children's Hospital / Washington University in St. Louis

Saint Louis, Missouri, 63130

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: University of California, San Francisco

Sabine Mueller, MD, PhD, MAS, PRINCIPAL_INVESTIGATOR, University of California, San Francisco
Robert Wechsler-Reya, PhD, STUDY_CHAIR, Columbia University
Margaret Shatara, MD, STUDY_CHAIR, Washington University School of Medicine
Megan Paul, MD, STUDY_CHAIR, Rady Children's Hospital
Lindsay Kilburn, MD, STUDY_CHAIR, Children's National Research 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 Date2022-02-22

Study Completion Date2028-01-31

Study Record Updates

Study Start Date2022-02-22

Study Completion Date2028-01-31

Terms related to this study

Keywords Provided by Researchers

Individualized Treatment Plan
Genetic Screening
Screening

Additional Relevant MeSH Terms

Medulloblastoma
Medulloblastoma, Childhood
Medulloblastoma Recurrent
Ependymoma
Ependymoma Malignant
Ependymoma of Brain