Molecular-Guided Therapy for Childhood Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Spectrum Health Hospitals
Sponsor:
Collaborators:
Translational Genomics Research Institute
Dell, Inc.
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT02162732
First received: June 11, 2014
Last updated: January 18, 2016
Last verified: January 2016
  Purpose
The purpose of this study is to test the feasibility (ability to be done) of experimental technologies to determine a tumor's molecular makeup. This technology includes a genomic report based on DNA exomes and RNA sequencing that will be used to discover new ways to understand cancers and potentially predict the best treatments for patients with cancer in the future.

Condition Intervention
Neuroblastoma
Medulloblastoma
Glioma
Ependymoma
Choroid Plexus Neoplasms
Craniopharyngioma
Dysembryoplastic Neuroepithelial Tumor
Meningioma
Primitive Neuroectodermal Tumors (PNETs)
Germ Cell Tumors
Rhabdomyosarcoma
Non-rhabdomyosarcoma
Ewings Sarcoma
Osteosarcoma
Wilms Tumor
Renal Cell Carcinoma
Malignant Rhabdoid Tumor
Clear Cell Sarcoma
Liver Tumors
Device: Guided Therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular-guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancers

Resource links provided by NLM:


Further study details as provided by Spectrum Health Hospitals:

Primary Outcome Measures:
  • Days to treatment will be used in order to determine feasibility of using tumor samples to assess genomic sequencing using predictive modeling to make real-time treatment decisions for children with relapsed/refractory cancers. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The definition of feasibility is: Enrollment onto study, genomic profile, analysis and report generation completed, tumor board held with treatment decision, treatment review completed, start of treatment, and completion of 1 cycle of therapy.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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, sub analysis examination of disease types, and biomarker development. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 Frame: 2 years ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 56
Study Start Date: June 2014
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Guided Therapy
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).
Device: Guided Therapy
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).

  Eligibility

Ages Eligible for Study:   13 Months to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects must have proven pediatric cancer with confirmation at diagnosis or at the time of recurrence/progression and clinical determination of disease for which there is no known effective curative therapy or disease that is refractory to established proven therapies fitting into one of the following categories:

    • Neuroblastoma- Patients that have relapsed following standard of care therapy (such as high risk patients, patient presenting after age 15 months or MYCN amplified, and only following (for eligible patients) high-dose chemotherapy followed by hematopoietic stem cell transplantation and maintenance therapy with retinoic acid and antibody therapy) or having progressed during standard of care therapy and non-responsive/progressive to accepted curative chemotherapy.
    • Brain Tumors
    • Medulloblastomas (At relapse after standard of care therapy [surgery, chemotherapy and/or radiation] and/or non-responsive/progressive on accepted curative therapy)
    • Gliomas (At relapse after standard of care therapy [surgery and/or radiation and/or chemotherapy] and/or non-responsive/progressive on accepted curative therapy)
    • Ependymomas (At relapse after standard of care therapy [surgery with or without radiation] and/or non-responsive/progressive on accepted curative therapy)
    • Choroid plexus tumors (At relapse after standard of care therapy [surgery] and/or non-responsive/progressive on accepted curative therapy)
    • Craniopharyngiomas (At relapse after standard of care therapy [surgery or suppressive therapy] and/or non-responsive/progressive on accepted curative therapy)
    • Dysembryoplastic neuroepithelial tumors (DNETs) (At relapse after standard of care therapy [surgery] and/or non-responsive/progressive on accepted curative therapy)
    • Meningiomas (At relapse after standard of care therapy [surgery] and/or non-responsive/progressive on accepted curative therapy)
    • Primitive Neuroectodermal Tumors (PNETs) (At relapse after standard of care therapy [surgery, chemotherapy, and/or radiation] and/or non-responsive/progressive on accepted curative therapy)
    • Germ cell tumors (At relapse after standard of care therapy [surgery, and/or radiation and/or chemotherapy] and/or non-responsive/progressive on accepted curative therapy)
    • Rare Tumors:
    • Soft tissue sarcoma Rhabdomyosarcoma (At relapse after standard of care therapy [surgery, and/or radiation, chemotherapy] and/or non-responsive/progressive to accepted curative chemotherapy) Non-rhabdomyosarcoma (At relapse after standard of care therapy [surgery, and/or radiation, chemotherapy] and/or non-responsive/progressive to accepted curative chemotherapy)
    • Bone Ewings sarcoma (At relapse after standard of care therapy [surgery, and/or radiation, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy) Osteosarcoma (At relapse after standard of care therapy [surgery, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy)
    • Renal Wilms tumor (At relapse after standard of care therapy [surgery, and/or radiation, chemotherapy] and/or non- responsive/progressive to accepted chemotherapy) Renal cell carcinoma (At relapse after standard of care therapy [surgery, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy) Malignant rhabdoid tumor (At diagnosis, as there is no known curative therapy) Clear Cell Sarcoma- (At relapse after standard of care therapy [radiation, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy) Germ Cell tumors (At relapse after standard of care therapy [surgery, chemotherapy] and/or non-responsive/progressive to accepted curative chemotherapy)
    • Liver Tumors (At relapse after standard of care therapy [surgery, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy)
  2. Subjects must be age >12 months at enrollment
  3. Subjects must be age ≤ 21 years at initial diagnosis
  4. Subjects must have measurable disease as demonstrated by residual abnormal tissue at a primary or metastatic site (measurable on CT or MRI) at the time of biopsy; tumor must be accessible for biopsy. In addition, subjects with bone or bone marrow only disease expected to be >75% tumor are eligible to enroll.
  5. Current disease state must be one for which there is currently no known effective therapy
  6. Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.
  7. Lansky or Karnofsky Score must be ≥ 50
  8. Subjects without bone marrow metastases must have an ANC > 750/μl to begin treatment.
  9. Subjects with CNS disease must have been on a stable dose of steroids for 2 weeks prior to their biopsy and must not have progressive hydrocephalus at enrollment.
  10. Adequate liver function must be demonstrated, defined as:

    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
    • ALT (SGPT) < 10 x upper limit of normal (ULN) for age
  11. A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
  12. 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.
  13. Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

  1. Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to biopsy
  2. 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).
  3. Subjects receiving any investigational drug concurrently.
  4. Subjects with uncontrolled serious infections or a life-threatening illness (unrelated to tumor)
  5. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02162732

Contacts
Contact: Genevieve Bergendahl, RN 616-267-0335 genevieve.bergendahl@helendevoschildrens.org
Contact: Alyssa VanderWerff 616-267-0327 alyssa.vanderwerff@helendevoschildrens.org

Locations
United States, Arkansas
Arkansas Children's Hospital Not yet recruiting
Little Rock, Arkansas, United States, 72202
Contact: Janet Storment, RN    501-364-2760    StormentJanetS@uams.edu   
Principal Investigator: Kathleen Neville, MD         
United States, California
Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Mehrzad Milburn    858-966-8155      
Principal Investigator: William Roberts, MD         
United States, Connecticut
Connecticut Children's Hospital Recruiting
Hartford, Connecticut, United States, 06106
Contact: Sharon Huie-White    860-545-9337    shuie@connecticutchildrens.org   
Principal Investigator: Nehal Parikh, MD         
United States, Florida
Arnold Palmer Hospital for Children Recruiting
Orlando, Florida, United States, 32806
Contact: Janice Hendrix    321-841-8588    Janice.Hendrix@orlandohealth.com   
Principal Investigator: Don Eslin, MD         
United States, Hawaii
Kapiolani Medical Center for Women and Children Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Andrea Siu, MPH    808-535-7169    andrea.siu@kapiolani.org   
Principal Investigator: Randal Wada, MD         
United States, Michigan
Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Shannon MacKeigan    616-267-1162    shannon.mackeigan@helendevoschildrens.org   
Principal Investigator: Deanna Mitchell, MD         
Principal Investigator: Giselle Sholler, MD         
United States, Minnesota
Children's Hospital and Clinics on Minnesota Recruiting
Minneapolis, Minnesota, United States, 55404
Contact: Courtney Haller    612-813-5913    courtney.haller@childrensmn.org   
Principal Investigator: Jawhar Rawwas, MD         
United States, Missouri
Children's Mercy Hospitals and Clinics Recruiting
Kansas City, Missouri, United States, 64108
Contact: Michelle Dinkins    816-302-6893    MDinkins@cmh.edu   
Principal Investigator: Keith August, MD         
Cardinal Glennon Children's Medical Center Recruiting
St. Louis, Missouri, United States, 63104
Contact: Katherine Maxwell, RN    314-268-4000      
Principal Investigator: William Ferguson, MD         
United States, New York
The Children's Hospital at Montefiore Recruiting
Bronx, New York, United States, 10467
Contact: Janeta Ivanova    718-741-2356    jivanova@montefiore.org   
Principal Investigator: Daniel Weiser, MD         
United States, North Carolina
Levine Children's Hospital Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Elizabeth Arroyo-Green    980-442-2312    Elizabeth.ArroyoGreen@carolinashealthcare.org   
Principal Investigator: Javier Oesterheld, MD         
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center and Children's Hospital Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Suzanne Treadway       streadway@hmc.psu.edu   
Principal Investigator: Valerie Brown, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Jacqueline Kraveka, MD    843-792-2957      
Principal Investigator: Jaqueline Kraveka, MD         
United States, Tennessee
Monroe Carrell Jr. Children's Hospital at Vanderbilt Recruiting
Nashville, Tennessee, United States, 37232
Contact: Natalie Resczenko    615-936-1522    natalie.resczenko@Vanderbilt.Edu   
Principal Investigator: Devang Pastakia, MD         
United States, Texas
Dell Children's Blood and Cancer Center Recruiting
Austin, Texas, United States, 78723
Contact: Letitia Holden, RN    512-628-1902    lholden@sfcaustin.com   
Principal Investigator: Sharon Lockhart, MD         
Texas Children's Cancer and Hematology Centers Not yet recruiting
Houston, Texas, United States, 77030
Contact: Patricia Chapa, BS    832-824-4393    prchapa@texaschildrens.org   
Principal Investigator: Peter Zage, MD, PhD         
United States, Utah
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Lisa Smith    801-662-4710    Lisa.Smith@imail.org   
Principal Investigator: Mark Fluchel, MD         
Sponsors and Collaborators
Giselle Sholler
Translational Genomics Research Institute
Dell, Inc.
Investigators
Study Chair: Giselle Sholler, MD NMTRC
  More Information

Additional Information:
Responsible Party: Giselle Sholler, NMTRC Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT02162732     History of Changes
Other Study ID Numbers: NMTRC009 
Study First Received: June 11, 2014
Last Updated: January 18, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Carcinoma, Renal Cell
Neuroblastoma
Neoplasms, Germ Cell and Embryonal
Rhabdomyosarcoma
Osteosarcoma
Ependymoma
Sarcoma, Ewing
Meningioma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Wilms Tumor
Liver Neoplasms
Craniopharyngioma
Adamantinoma
Rhabdoid Tumor
Sarcoma, Clear Cell
Neoplasms, Neuroepithelial
Choroid Plexus Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on August 29, 2016