Patient case: 26-year-old male with Liposarcoma. Genetic variant: MDM2 Amplification. Other conditions: None.

Clinical trial: Molecular-Guided Therapy for Childhood Cancer

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: 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

Relevance to patient case: not relevant