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Molecular-Guided Therapy for Relapsed and Refractory Childhood Cancer

Primary Purpose

Neuroblastoma, Medulloblastoma, Brain Tumors

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Guided Therapy- Pediatric Gene Analysis Platform
Sponsored by
Giselle Sholler
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma

Eligibility Criteria

13 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must have histologically proven neuroblastoma, brain tumor, or rare tumor and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression
  • Subjects must be age >12 months at enrollment.
  • Subjects must be age ≤ 21 years at initial diagnosis.
  • Subjects must have measurable disease as demonstrated by residual abnormal tissue at a primary or metastatic site measuring more than 1 cm in any dimension by standardized imaging (CT or MRI); tumor must be accessible for biopsy. Patients with bone marrow only disease expected to be >75% tumor are eligible to enroll.
  • Current disease state must be one for which there is currently no known curative therapy
  • Lansky or Karnofsky Score must be more than 50
  • Subjects without bone marrow metastases must have an ANC > 750/μl
  • Adequate liver function must be demonstrated, defined as:

    1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
    2. SGPT (ALT) < 10 x upper limit of normal (ULN) for age
  • A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
  • Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
  • Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines. Voluntary consent for optional biology studies will be included.

Exclusion Criteria:

  • Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to enrollment and 14 days prior to study treatment start date.
  • Subjects who have received any radiotherapy to the primary sample site within the last 14 days (radiation may be included in treatment decision after biopsy).
  • Subjects receiving anti-tumor therapy for their disease or any investigational drug concurrently
  • Subjects with serious infection or a life-threatening illness (unrelated to tumor) that is > Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring parenteral antibiotic therapy.
  • Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study

Sites / Locations

  • Phoenix Children's Hospital
  • Rady Children's Hospital
  • Connecticut Children's Hospital
  • Arnold Palmer Hospital for Children- MD Anderson
  • Kapiolani Medical Center for Women and Children
  • Helen DeVos Children's Hospital
  • Children's Mercy Hospitals and Clinics
  • Cardinal Glennon Children's Medical Center
  • Levine Children's Hospital
  • Medical University of South Carolina
  • Vanderbilt-Ingram Cancer Center
  • Dell Children's Blood and Cancer Center
  • Primary Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Guided Therapy- Pediatric Gene Analysis Platform

Arm Description

A total of 48 neuroblastoma, brain tumor, and rare tumor patients who are refractory or relapsed on conventional therapy will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).

Outcomes

Primary Outcome Measures

Days to treatment will be used in order to determine feasibility of using tumor samples to assess genomic mRNA expression arrays and DNA Mutation Panels using predictive modeling
The definition of feasibility for this study will include: "Enrollment onto study, RNA expression profile completed, DNA Mutation Panel completed, genomic analysis and report generation, tumor board held with treatment decision, treatment review completed and start of treatment by 21 days post biopsy/surgical resection date, and then completion of 1 cycle of therapy."

Secondary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety
To determine the safety of allowing a molecular tumor board to determine individualized treatment plans
Overall Response Rate (ORR) of Participants by the presence of radiologically assessable disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans.
To determine the activity of treatments chosen based on Overall response rate (ORR) using RESIST criteria. The assessment of response will include the initial measurable targets and will be performed after cycle 2, then after every other cycle.
Duration of response will be objectively documented
Duration of response, defined as the period of time from when measurement criteria are met for complete response (CR) or partial response (PR), whichever is first recorded, until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started)
Biology studies to include: genomic analysis of cells pre- and post- treatment, correlation of in vitro response to in vivo response, flow cytometry of tumor burden in bone marrow and biomarker development
To explore the relationship between tumor phenotype and response by permitting use of tumor tissue in a correlative biologic study
Progression Free Survival (PFS) interval will be measured by days and compared to the PFS of previous chemotherapy regimens since relapse for each patient.
Time to progression (PFS), defined as the period from the start of the treatment until the criteria for progression are met taking as reference the screening measurements

Full Information

First Posted
February 26, 2013
Last Updated
September 26, 2023
Sponsor
Giselle Sholler
Collaborators
Dell, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01802567
Brief Title
Molecular-Guided Therapy for Relapsed and Refractory Childhood Cancer
Official Title
A Feasibility Trial Using Molecular-Guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2013 (undefined)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Giselle Sholler
Collaborators
Dell, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to test the feasibility (ability to be done) of experimental technologies to determine a tumor's molecular makeup (gene expression profile) and mutations. This technology called the "Pediatric Gene Analysis Platform" includes a genomic report (gene expression profile) and a DNA Mutation Panel Report that are being used to discover new ways to understand cancers and potentially predict the best treatments for patients with cancer in the future.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Medulloblastoma, Brain Tumors, Rare Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Guided Therapy- Pediatric Gene Analysis Platform
Arm Type
Experimental
Arm Description
A total of 48 neuroblastoma, brain tumor, and rare tumor patients who are refractory or relapsed on conventional therapy will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).
Intervention Type
Device
Intervention Name(s)
Guided Therapy- Pediatric Gene Analysis Platform
Other Intervention Name(s)
Molecular Guided Therapy
Intervention Description
A total of 48 neuroblastoma, brain tumor, and rare tumor patients who are refractory or relapsed on conventional therapy will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).
Primary Outcome Measure Information:
Title
Days to treatment will be used in order to determine feasibility of using tumor samples to assess genomic mRNA expression arrays and DNA Mutation Panels using predictive modeling
Description
The definition of feasibility for this study will include: "Enrollment onto study, RNA expression profile completed, DNA Mutation Panel completed, genomic analysis and report generation, tumor board held with treatment decision, treatment review completed and start of treatment by 21 days post biopsy/surgical resection date, and then completion of 1 cycle of therapy."
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of Participants with Adverse Events as a Measure of Safety
Description
To determine the safety of allowing a molecular tumor board to determine individualized treatment plans
Time Frame
2 years
Title
Overall Response Rate (ORR) of Participants by the presence of radiologically assessable disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans.
Description
To determine the activity of treatments chosen based on Overall response rate (ORR) using RESIST criteria. The assessment of response will include the initial measurable targets and will be performed after cycle 2, then after every other cycle.
Time Frame
2 years
Title
Duration of response will be objectively documented
Description
Duration of response, defined as the period of time from when measurement criteria are met for complete response (CR) or partial response (PR), whichever is first recorded, until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started)
Time Frame
2 years
Title
Biology studies to include: genomic analysis of cells pre- and post- treatment, correlation of in vitro response to in vivo response, flow cytometry of tumor burden in bone marrow and biomarker development
Description
To explore the relationship between tumor phenotype and response by permitting use of tumor tissue in a correlative biologic study
Time Frame
2 years
Title
Progression Free Survival (PFS) interval will be measured by days and compared to the PFS of previous chemotherapy regimens since relapse for each patient.
Description
Time to progression (PFS), defined as the period from the start of the treatment until the criteria for progression are met taking as reference the screening measurements
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have histologically proven neuroblastoma, brain tumor, or rare tumor and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression Subjects must be age >12 months at enrollment. Subjects must be age ≤ 21 years at initial diagnosis. Subjects must have measurable disease as demonstrated by residual abnormal tissue at a primary or metastatic site measuring more than 1 cm in any dimension by standardized imaging (CT or MRI); tumor must be accessible for biopsy. Patients with bone marrow only disease expected to be >75% tumor are eligible to enroll. Current disease state must be one for which there is currently no known curative therapy Lansky or Karnofsky Score must be more than 50 Subjects without bone marrow metastases must have an ANC > 750/μl Adequate liver function must be demonstrated, defined as: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND SGPT (ALT) < 10 x upper limit of normal (ULN) for age A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses) Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended. Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines. Voluntary consent for optional biology studies will be included. Exclusion Criteria: Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to enrollment and 14 days prior to study treatment start date. Subjects who have received any radiotherapy to the primary sample site within the last 14 days (radiation may be included in treatment decision after biopsy). Subjects receiving anti-tumor therapy for their disease or any investigational drug concurrently Subjects with serious infection or a life-threatening illness (unrelated to tumor) that is > Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring parenteral antibiotic therapy. Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giselle Sholler, MD
Organizational Affiliation
Beat Childhood Cancer at Atrium Health
Official's Role
Study Chair
Facility Information:
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Connecticut Children's Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Arnold Palmer Hospital for Children- MD Anderson
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Kapiolani Medical Center for Women and Children
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Helen DeVos Children's Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Children's Mercy Hospitals and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Dell Children's Blood and Cancer Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.beatcc.org
Description
Beat Childhood Cancer Consortium website

Learn more about this trial

Molecular-Guided Therapy for Relapsed and Refractory Childhood Cancer

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