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

Summary

This study is being conducted in order to determine the safety, dose-limiting toxicities, and maximum tolerated dose of cabozantinib in combination with 13-cis-retinoic acid in patients with relapsed or refractory solid tumors including tumors of the central nervous system (CNS)

Eligibility

Inclusion 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

5 Steroids are permitted for control of emesis and for symptom management in patients with intracranial metastases. However, patients with known CNS disease or CNS metastases who require increasing doses of steroids are not allowed in the study. Patients MUST be on a stable or decreasing steroid dose for greater than or equal to 1 week prior to start of study therapy.

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

Exclusion Criteria:

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

Conditions2

Locations2 sites

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