Clinical trial NCT02162732: Molecular-Guided Therapy for Childhood Cancer
Official title: Molecular-guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: Translational Genomics Research Institute
name: Dell, Inc.
First posted: 2014-06-13
Enrollment: 186
Sex: ALL
Minimum age (years): 13
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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. 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.


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

Primary outcomes:
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.
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants With an Unexpected Adverse Events as a Measure of Safety
timeFrame: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 4 years.
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.
timeFrame: Followed until off therapy, generally 4 years
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.
timeFrame: From date of start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Hartford
country: United States
facility: Connecticut Children's Hospital
state: Connecticut
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospital and Clinics on Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Portland
country: United States
facility: Randall Children's Hospital
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center and Children's Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carrell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Blood and Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer and Hematology Centers
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
Study officials:
affiliation: Beat Childhood Cancer at Atrium Health
name: Giselle Sholler, MD
role: STUDY_CHAIR
References: