Cabozantinib in Combination With 13-cis-Retinoic Acid in Children With Relapsed or Refractory Solid Tumors

Eligibility Criteria

• 1. Patients must have had histologic verification of a solid tumor, including tumors of the CNS, at the time of initial diagnosis or relapse, with disease that has progressed on standard therapy, relapsed after standard therapy, or for which no standard curative therapy is known
• 2. Patients must have documentation of either measurable or evaluable disease within 4 weeks of onset of study therapy
• 3. Performance Status - Lansky play or Karnofsky score of ≥40
• 4. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrolment with the exception of hematologic parameters (absolute neutrophil count, hemoglobin, platelet count), which need to have recovered to meet eligibility criteria
• 6. Female subjects of childbearing potential must agree to use an adequate method of contraception for the course of the study. Male subjects must agree to use an adequate method of contraception for the course of the study
• 1. Evidence of severe or uncontrolled systemic disease
• 2. Cardiac Disease
• 3. Blood pressure \>95th percentile for age (either systolic or diastolic) or \>140/90 for patients \>18 years of age and uncontrolled by oral medication at onset of study therapy
• 4. Women who are currently pregnant or breastfeeding.
• 5. Prior therapy with cabozantinib at any time.
• 6. Major surgery within 8 weeks before starting study therapy.
• 7. Prior treatment with allogeneic stem cell transplantation or total body irradiation (TBI)
• 8. Therapeutic anticoagulation with heparin, LMWH , or any other agents are not allowed in subjects with intracranial tumors/metastatses.
• 9. Concomitant anticoagulation at therapeutic doses with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel) in patients without primary or metastatic CNS tumors
• 10. The subject has experienced any of the following:
• 1. clinically-significant GI bleeding within 6 months before the first dose of study treatment;
• 2. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.
• 11. The subject has radiographic evidence of cavitating pulmonary lesion(s) and/or the subject has tumor invading any major blood vessels;
• 12. The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
• 13. thromboembolic event requiring therapeutic anticoagulation within 6 months of onset of study treatment
• 14. GI disorders particularly those associated with a high risk of perforation or fistula formation
• 15. Inability to swallow intact tablets