A Study of Cabozantinib as a Maintenance Agent to Prevent Progression or Recurrence in High-Risk Pediatric Solid Tumors

NCT05135975 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CaboMain
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 6

Brief Summary

This study will expand the types of pediatric cancers being evaluated for response to cabozantinib. The current COG study is restricted to Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, Wilms tumor, and a handful of uncommon tumors. The proposed study will extend this evaluation to tumors that have been shown to either express known targets of cabozantinib or with preclinical evidence of efficacy, including specifically neuroblastomas. These tumors have high morbidity and mortality, particularly in the relapse setting, and few or no proven therapeutic options. As such, evaluation of cabozantinib in these studies is warranted. The study hypothesizes that use of cabozantinib in patients with ultra-high-risk pediatric solid tumors with minimal disease burden, as defined in the inclusion criteria below, can prevent and/or slow recurrent tumor formation in pediatric solid tumors and thereby significantly extend the period of disease control and/or induce a durable cure.

Conditions

Neuroblastoma; Sarcoma

Keywords

Malignant rhabdoid tumor; Osteosarcoma; Ewing sarcoma; Rhabdomyosarcoma; Desmoplastic small round blue cell tumor; Wilms tumor; Solid tumor; Metastatic osteosarcoma

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of oral daily cabozantinib, administered for up to 12 months, on the one-year progression-free survival of patients with "ultra-high-risk" pediatric solid tumors.

  Defined as the time from diagnosis until the date of disease progression

  4 years

Secondary Outcomes (4)

• To evaluate the effect of oral daily cabozantinib on the one-, two-, and five-year overall survival of patients with "ultra-high-risk" pediatric solid tumors.

  5-8 years

• To evaluate the effect of oral daily cabozantinib on the two- and five-year progression- free survival of patients with "ultra-high-risk" pediatric solid tumors.

  8 years

• To evaluate the duration of response to cabozantinib, both during drug administration and after discontinuation of cabozantinib at study-defined time points.

  4 years

• To evaluate the incidence of adverse events associated with the use of cabozantinib in this population when taken for up to 12 months.

  4 years

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Enrolled patients will be treated with cabozantinib maleate, tablet formulation, using the recommended Phase 2 dose of 40 mg/m2/day, to a maximum of 420 mg/week. Treatment will be administered in 28- day cycles.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Enrolled patients will be treated with cabozantinib maleate, tablet formulation, using the recommended Phase 2 dose of 40 mg/m2/day to a maximum of 420 mg/week. Treatment will be administered in 28- day cycles.

Cabozantinib

Eligibility Criteria

• Age: 18 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• Exelixis: collaborator

Study Sites (6)

Children's Hospital of Alabama/UAB

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Sarcoma; Rhabdoid Tumor; Osteosarcoma; Sarcoma, Ewing; Rhabdomyosarcoma; Wilms Tumor

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms, Complex and Mixed; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Nilay Shah, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madeline Richardson, MA

CONTACT

6147222739; Madeline.Richardson3@nationwidechildrens.org

Parth Patel, MPH, CCRP

CONTACT

6147224319; parth.patel2@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2021
• First Posted: November 26, 2021
• Study Start: July 20, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 12, 2025

Record last verified: 2025-08

Locations

US (6)