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Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma (PNOC027)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05057702
Recruitment Status : Not yet recruiting
First Posted : September 27, 2021
Last Update Posted : November 9, 2021
Sponsor:
Collaborators:
Washington University School of Medicine
St. Baldrick's Foundation
Ashion Analytics
University of Washington
Pacific Pediatric Neuro-Oncology Consortium
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
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 of performing real-time drug screening on tissue taken during surgery, 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 medulloblastoma 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.

Condition or disease Intervention/treatment Phase
Medulloblastoma Medulloblastoma, Childhood Medulloblastoma Recurrent Other: Specialized Tumor Board Treatment Plan Not Applicable

Detailed Description:

This is a single arm multi-center pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). Relapsed participants will receive an individualized treatment recommendation including up to four FDA-approved drugs based on the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

PRIMARY OBJECTIVE:

I. To determine the feasibility of using the results of real-time in vitro drug screening, whole exome sequencing, and RNA sequencing of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma.

SECONDARY OBJECTIVE:

I. To determine the safety and describe the toxicity of treating children and young adults with relapsed medulloblastoma according to a specialized tumor board that makes treatment recommendations based on real-time drug screening and genomic sequencing.

EXPLORATORY OBJECTIVES:

I. To estimate the objective response rate, progression free survival at 6 months (PFS-6) and overall survival (OS) of relapsed medulloblastoma in children and young adults treated with an individualized treatment regimen.

II. To assess Quality of Life (QOL) measures in participants with relapsed medulloblastoma treated with an individualized regimen.

III. To archive tumor and normal DNA from each participant along with serial blood draw following therapies as biospecimens for later studies to determine whether circulating tumor DNA (ctDNA) sequences in the participant's blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance.

Participants may continue treatment as tolerated for up to two years or until disease progression. Participants will be followed until progression, death, or up to 5 years from start of therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Pilot Trial of Real Time Drug Screening and Genomic Testing to Determine an Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma
Estimated Study Start Date : November 30, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : January 31, 2027


Arm Intervention/treatment
Experimental: Individualized Treatment Recommendation
Participants will receive an individualized treatment recommendation including a combination of up to four FDA-approved drugs within 21 business days of tissue acquisition using the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.
Other: Specialized Tumor Board Treatment Plan
Specialized Treatment Plan of up to four FDA approved drugs based on participant's screening results will be assigned by PNOC specialized tumor board
Other Names:
  • Individualized Treatment Plan
  • Specialized Treatment Plan




Primary Outcome Measures :
  1. Median Time from tissue collection to issued treatment plan from the specialized tumor board [ Time Frame: Up to 21 days ]
    Time to tissue collection will be used to determine the feasibility of using the results of real-time in vitro drug screening, WES and RNAseq of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma. Participants are expected to receive treatment plan within 21 business days


Secondary Outcome Measures :
  1. Proportion of participants with Adverse Events [ Time Frame: Up to 2 years ]
    Proportion of participants with grade 3 or higher toxicities classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3 or higher criteria will be summarized by maximum grade and relationship to study drug(s).



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants must have recurrent medulloblastoma.
  2. Participants must have surgically accessable disease.
  3. Prior Therapy:

    1. The participant must have recurrent medulloblastoma following at least one prior therapy for initial diagnosis or previous recurrence- surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy - prior to study registration.
    2. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

      • Myelosuppressive chemotherapy: Participants must have received their last dose of known myelosuppressive anti-cancer chemotherapy at least 3 weeks prior to study registration (6 weeks prior if nitrosourea).
      • Biologic agent: Participant must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent no less than 7 days prior to study registration.
      • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
      • For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
      • Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such participants should be discussed with the study chair prior to registration. For bevacizumab, participants must have received last dose > 32 days prior to study registration.
      • Bone Marrow Transplant: Participant must be >= 6 months since allogeneic bone marrow transplant prior to registration and >=3 months since autologous bone marrow/stem cell prior to registration.
  4. Participant must be a candidate for surgical resection or biopsy. Minimum tissue requirements for study are defined in Section 9.1.
  5. Radiation - Participants must have:

    1. Had their last fraction of local irradiation to primary tumor >= 12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
    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: Subjects 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) >= 1000/mm3
      • Platelet count >= 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
    2. Adequate Renal Function Defined as:

      • Creatinine clearance or radioisotope GFR >= 70 milliliter/minute (mL/min) /1.73 m2 or
      • A serum creatinine based on age/sex as follows:

      Age / Maximum Serum Creatinine (mg/dL) Male / Maximum Serum Creatinine (mg/dL) Female.

      • 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:

      • Bilirubin (sum of conjugated and unconjugated) <= 1.5 x upper limit of normal (ULN) for age.
      • Serum glutamic-pyruvic transaminase (SGPT) / alanine aminotransferase (ALT) <= 110 U/L.
      • Serum albumin >= 2 g/dL.
  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 she is pregnant while she or her partner is participating in this study, she should inform her treating physician 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. A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Exclusion Criteria:

  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.

Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05057702


Contacts
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Contact: Aubrie Drechsler 415-502-1600 PNOC027@ucsf.edu

Locations
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United States, California
Rady Children's Hospital
San Diego, California, United States, 92123
Principal Investigator: John Crawford, MD, MS         
Sub-Investigator: Jennifer Elster, MD         
University of California, San Francisco
San Francisco, California, United States, 94143
Contact: Aubrie Drechsler    415-502-1600    PNOC027@ucsf.edu   
Principal Investigator: Sabine Mueller, MD, PhD         
Sub-Investigator: Alyssa Reddy, MD         
United States, Missouri
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
Sub-Investigator: Mohamed Abdelbaki, MD         
Principal Investigator: Josh Rubin, MD, PhD         
Sponsors and Collaborators
University of California, San Francisco
Washington University School of Medicine
St. Baldrick's Foundation
Ashion Analytics
University of Washington
Pacific Pediatric Neuro-Oncology Consortium
Investigators
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Principal Investigator: Sabine Mueller, MD, PhD, MAS University of California, San Francisco
Study Chair: Joshua Rubin, MD, PhD Washington University School of Medicine
Study Chair: Robert Wechsler-Reya, PhD Sanford Burnham Prebs Medical Discovery Institute
Study Chair: Margaret Shatara, MD Washington University School of Medicine
Study Chair: Megan Paul, MD Rady Children's Hospital
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT05057702    
Other Study ID Numbers: 21083
NCI-2021-09726 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
First Posted: September 27, 2021    Key Record Dates
Last Update Posted: November 9, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data after de-identification.
Supporting Materials: Study Protocol

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, San Francisco:
Individualized Treatment Plan
Genetic Screening
Screening
Additional relevant MeSH terms:
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Medulloblastoma
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