NCT05135975

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

Phase 2 Study of Cabozantinib as a Maintenance Agent to Prevent Progression or Recurrence in High-Risk Pediatric Solid Tumors

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 86 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 18 Months – 40 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The study hypothesizes that use of cabozantinib in patients with ultra-high-risk pediatric solid tumors who have achieved and maintained (for at least 4 weeks) a "best response" to their most recent line of therapy, as defined in the inclusion criteria below, can prevent and/or slow recurrent tumor formation in pediatric solid tumors, improve one-year progression-free survival by 20% as compared to historical controls, and also improve longer-term progression-free and overall survival without significant impact on quality of life. We also hypothesize, in an exploratory aim, that there will be improvement in two-year progression free survival in patients with metastatic Ewing sarcoma and osteosarcoma specifically. The study proposes to evaluate the efficacy of up to one year of treatment with cabozantinib in pediatric solid tumors after completion of last therapy with a "best response." There are multiple reasons for this approach, as opposed to continual therapy until toxicity or disease progression alone. First, for most of these ultra-high-risk diseases, the greatest risk of recurrence has historically been within 12 months after last therapy, and often times considerably sooner. As such, we should be able to evaluate a meaningful difference within 12 months. Second, the goal of this study is to evaluate if, during a critical period of disease control, use of cabozantinib can induce a durable remission. There are active Phase 2 and 3 studies of cabozantinib, including with the Children's Oncology Group, evaluating the efficacy of cabozantinib in controlling pediatric cancers with measurable burden of disease. However, we know that, in patients with "ultra-high-risk" disease who have achieved a best response including stable disease, partial response or even complete response, there is still active disease with high risk of growth, as demonstrated in the studies cited above. Our study seeks to augment ongoing work in pediatric cancers by testing the hypothesis that cabozantinib can durably silence cancer cell viability after a best response to prior treatment. Third, this work would mark a fundamental change in the indication for use of cabozantinib in pediatric cancers, broadening its utility from a "rescue" agent to a maintenance therapy that may be critical for disease control, during either primary or secondary remission. 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.

Conditions

• Neuroblastoma
• Sarcoma

Interventions

Type	Name	Description
DRUG	Cabozantinib	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.

Timeline

• Start date: 2022-07-20
• Primary completion: 2026-07-01
• Completion: 2029-12-01
• First posted: 2021-11-26
• Last updated: 2025-08-12

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study