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

NCT03611595 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 171971
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief 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)

Conditions

Solid Tumor

Keywords

13-cis-Retinoic Acid; Children; Relapsed Solid Tumors; Refractory Solid Tumors; Solid Tumors; cancer; cabozantinib

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose of cabozantinib plus 13-cis-retinoic acid

  3+3 design to find the maximum tolerated dose (MTD) of cabozantinib when used in combination with 13-cis-retinoic acid

  12 months

Study Arms (1)

Cabozantinib and 13-cis-retinoic acid

EXPERIMENTAL

Cabozantinib will be given orally once every day with cycles repeated every 4 weeks (28 days, +/- 3 days), with no rest periods between cycles, combined with 13-cis-retinoic acid at 80mg/m2/dose twice daily for two consecutive weeks (14 days) out of every four weeks (28 days, +/- 3 days).

Drug: Cabozantinib; Drug: 13-cis-retinoic acid

Interventions

Cabozantinib DRUG

Cabozantinib will be given orally once every day with cycles repeated every 4 weeks (28 days, +/- 3 days), with no rest periods between cycles

Also known as: CABOMETYX

Cabozantinib and 13-cis-retinoic acid

13-cis-retinoic acid DRUG

13-cis-retinoic acid at 80mg/m2/dose twice daily for two consecutive weeks (14 days) out of every four weeks (28 days, +/- 3 days).

Also known as: isotretinoin

Cabozantinib and 13-cis-retinoic acid

Eligibility Criteria

• Age: 2 Years - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Patients must have documentation of either measurable or evaluable disease within 4 weeks of onset of study therapy
• Performance Status - Lansky play or Karnofsky score of ≥40
• 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
• 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.
• \. 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

You may not qualify if:

• Evidence of severe or uncontrolled systemic disease
• Cardiac Disease
• 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
• Women who are currently pregnant or breastfeeding.
• Prior therapy with cabozantinib at any time.
• Major surgery within 8 weeks before starting study therapy.
• Prior treatment with allogeneic stem cell transplantation or total body irradiation (TBI)
• Therapeutic anticoagulation with heparin, LMWH , or any other agents are not allowed in subjects with intracranial tumors/metastatses.
• 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
• The subject has experienced any of the following:
• clinically-significant GI bleeding within 6 months before the first dose of study treatment;
• any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.
• The subject has radiographic evidence of cavitating pulmonary lesion(s) and/or the subject has tumor invading any major blood vessels;
• 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
• thromboembolic event requiring therapeutic anticoagulation within 6 months of onset of study treatment

Sponsors & Collaborators

• Peter Zage: lead
• Exelixis: collaborator

Study Sites (2)

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

cabozantinib; Isotretinoin

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Peter Zage

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Zage, MD

CONTACT

858-534-6494; pzage@ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor-in-Residence

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: August 2, 2018
• Study Start: August 28, 2018
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 28, 2025

Record last verified: 2025-08

Locations

US (2)