Clinical Trials /

Molecular-Guided Therapy for Childhood Cancer

NCT02162732

Description:

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.

Related Conditions:
  • Central Nervous System Neoplasm
  • Choroid Plexus Neoplasm
  • Craniopharyngioma
  • Dysembryoplastic Neuroepithelial Tumor
  • Ependymoma
  • Ewing Sarcoma
  • Germ Cell Tumor
  • Glioma
  • Kidney Wilms Tumor
  • Medulloblastoma
  • Meningioma
  • Neuroblastoma
  • Neuroectodermal Tumor of Soft Tissue
  • Soft Tissue Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Molecular-Guided Therapy for Childhood Cancer
  • Official Title: Molecular-guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancers

Clinical Trial IDs

  • ORG STUDY ID: NMTRC009
  • NCT ID: NCT02162732

Conditions

  • 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

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.

Trial Arms

NameTypeDescriptionInterventions
Guided TherapyExperimentalA total of 200 neuroblastoma, brain tumor, and rare tumor patients 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 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
          
    Maximum Eligible Age:21 Years
    Minimum Eligible Age:13 Months
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure: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
    Safety Issue:
    Description: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

    Measure:Number of Participants with Adverse Events as a Measure of Safety
    Time Frame:2 years
    Safety Issue:
    Description:To determine the safety of allowing a molecular tumor board to determine individualized treatment plans
    Measure: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
    Safety Issue:
    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.
    Measure:Duration of response will be objectively documented
    Time Frame:5 years
    Safety Issue:
    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)
    Measure: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
    Safety Issue:
    Description:To explore the relationship between tumor phenotype and response by permitting use of tumor tissue in a correlative biologic study
    Measure: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
    Safety Issue:
    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

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Giselle Sholler

    Last Updated

    July 7, 2017