• Age: ≥ 18 months of age and \<40 years of age at time of study enrollment

• Performance level: Patients must have a Lansky or Karnofsky performance status score of ≥ 50, corresponding to ECOG categories 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are upright in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Patients should also have recovery to baseline or ≤ Grade 1 CTCAE v4.03 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (see Section 3.2.3, criteria 4)

• Patient Body Surface Area (BSA): Patients must be ≥0.35 m2 in BSA, using the Mosteller formula, BSA = (((Height in cm) \* (Weight in kg))/ 3600)½ within two weeks of study enrollment

• Prior therapy: patients must have recovered from the acute toxic effects of prior therapy, with the following time specifications:

∙ Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment on study (6 weeks if prior therapy included nitrosourea)

‣ Other medicinal anti-cancer agents: Patients must not have received non-myelosuppressive anticancer agents, including any type of small molecule kinase inhibitor, within 14 days of enrollment on study

‣ Biological anticancer therapy (including antibody therapy or cellular therapy): Patients must not have received biological anticancer therapy within 21 days of enrollment on study

‣ Radiation therapy: Patients must not have received external beam radiation therapy to sites outside of the lungs within 2 weeks of study enrollment, external beam radiation therapy to sites within the lungs within 4 weeks of study enrollment, or I-131 MIBG therapy within 6 weeks of study enrollment. Subjects with clinically relevant ongoing complications from prior radiation therapy MUST be discussed with Study Chair or his proxy to determine suitability and safety of enrollment.

‣ Myeloablative therapy: Patients must not have received myeloablative therapy within 2 months of study enrollment, must not have received a blood stem cell/marrow infusion within 3 weeks of study enrollment, and must have attained blood count recovery as per Section 3.2.3, criteria 5

• Bone Marrow Function: Patients must have adequate bone marrow function at time of study enrollment, as defined as:

∙ Absolute neutrophil count (ANC) ≥1000/mcL; patients cannot have received filgrastim, pegfilgrastim or equivalent biosimilar within 14 days of study enrollment

‣ Platelet count ≥ 100,000/mcL; patients can receive no more than 15 mL/kg of platelet transfusions per week at time of enrollment to meet the parameters; patients can receive a TPO agonist (e.g., eltrombopag or romiplostim) at time of enrollment but must be on a stable dose for at least 14 days prior to enrollment

‣ Hemoglobin ≥ 8.0 g/dL; patients can receive no more than 10 mL/kg of packed red blood cells (PRBCs)/week transfused at time of enrollment on therapy to meet the parameters; patients may receive erythropoietin or biosimilar equivalent but must have been on a stable dose and not require PRBC transfusions for at least 14 days prior to study enrollment

‣ Patients with residual bone marrow metastases at end of most recent line of therapy must have stable disease or better at two bone marrow evaluations at least 4 weeks apart, with the second marrow assessment at least 4 weeks after end of most recent therapy. Stable disease is defined as \<2-fold change in marrow burden between the two timepoints and ≤20% marrow involvement. When bilateral bone marrow assessment is performed, average marrow involvement of the two sites will be used for eligibility.

• Renal Function: Patient must meet criteria for both a. and b. below to have adequate renal function, within 2 weeks of study enrollment

∙ Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2, as per institutional standard testing OR serum creatinine based on age/gender as listed in protocol:

‣ Urine protein: ≤ 30 mg/dl in urinalysis (clean catch recommended), equivalent to ≤ 1+ on dipstick OR quantitative urine protein \< 1000 mg in a 24hr urine sample. NOTE: If the initial urinalysis shows \>30 mg/dL urine protein (or \> 1+ on dipstick), a 24-hour quantitative urine protein should be utilized, as described above, for eligibility consideration.

• Hepatic function: Patient must meet ALL of the below criteria, within 14 days of study enrollment, to have adequate hepatic function:

∙ Total bilirubin \< 2x institutional upper limit of normal (ULN) for age

‣ ALT\<5x ULN

‣ Serum albumin \>2.7 g/dL

• Cardiovascular Function: Patients must have adequate cardiovascular function as defined as:

∙ No significant arrhythmias, strokes, transient ischemic attacks, or myocardial infarction within 6 months of study enrollment

‣ QTc ≤ 480 msec within 7 days of study enrollment (calculated using Bazett calculation or Fridericia calculation as per institutional standard of care; whichever calculation is used for eligibility must be used for all future QTc calculations).

∙ A single ECG with QTc meeting the above criterion is adequate. However, if an initial ECG shows a QTc \>480 ms, obtain two additional ECGs with each ECG at least 30 minutes apart. Calculate each individual QTc by the same calculation method and average the values; the resulting average QTc will be used for eligibility.

‣ Blood pressure ≤ 95th percentile for age, height, and gender for patients \<18 years of age (78), or BP ≤140/90 for patients ≥18 years of age. At time of enrollment, patients may be on one antihypertensive agent at a stable dose for at least 2 weeks prior to enrollment.

• Pancreatic function: Patient must have adequate pancreatic function, as defined by a serum lipase \<2x ULN

⁃ Neurologic function: Patients with defined seizures who are on a stable anti- convulsant regimen using drugs that do not induce hepatic metabolizing enzymes for at least 4 weeks are eligible for enrollment Recommended Non-enzyme inducing anticonvulsants Clonazepam Diazepam Ethosuximide Ezogabine Gabapentin Lacosamide Lamotrigine Levetiracetam Lorazepam Perampanel Tiagabine Topiramate Valproic Acid Zonisamide Unacceptable Enzyme inducing anticonvulsants Carbamazepine Felbamate Phenobarbital Fosphenytoin Phenytoin Primidone Oxcarbazepine

⁃ Lung integrity: Patients must not have had any invasive pulmonary procedure (including bronchoalveolar lavage, lung biopsy, transbronchial biopsy, or thoracotomy) or pneumothorax within 4 weeks of enrollment on study.

⁃ Surgeries or trauma:

• Patients must not have had any major surgical procedures, laparoscopic procedures, sepsis, shock, or physical trauma requiring hospitalization within 4 weeks of enrollment on study. The primary surgeon of any major surgical procedures must authorize antineoplastic treatment before enrollment on study.

∙ Patients must not have had a central line or subcutaneous port placement, revision, or removal (excluding a peripherally inserted central catheter (PICC)) within 7 days of study enrollment. Advise patients with a surgically placed central line or subcutaneous port that removal of the port once enrolled on study would require holding study treatment for 4 weeks prior, and surgical removal of the central line or port would be recommended to be performed prior to cabozantinib initiation.

∙ Patients must not have had a core or fine needle biopsy within 7 days of study enrollment.

∙ Any surgical wounds or incisions must be healed, as determined by treating physician, prior to enrollment on study.

∙ Bone marrow aspiration and/or biopsy are not considered surgical procedures for the purpose of this study.

⁃ Patients must be able to swallow tablets intact. Tablets cannot be cut or crushed.

⁃ Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment. Post-menarchal females must be confirmed to not be pregnant at time of enrollment.

⁃ Patient or legal guardian must be capable of understanding and complying with the protocol requirements and must have signed the informed consent document.

⁃ Patient must be able to start study treatment no later than 12 weeks after end of prior therapy, where 1 week = 7 days.

⁃ Patient must be enrolled on study within 14 days of qualifying radiographic imaging studies demonstrating best response as per Section 3.1.2.

⁃ Patient must be able to start study treatment no later than 7 days from study enrollment.