NCT04079712

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors

A Phase 2 Study of XL184 (Cabozantinib) in Combination With Nivolumab and Ipilimumab for the Treatment of Poorly Differentiated Neuroendocrine Carcinomas

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well the combination of XL184 (cabozantinib), nivolumab, and ipilimumab work in treating patients with poorly differentiated neuroendocrine tumors (i.e., neuroendocrine tumor that does not look like the normal tissue it arose from). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab and ipilimumab may shrink the cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the overall response rate (ORR) associated with the combination of XL184 (cabozantinib), nivolumab, and ipilimumab in patients with advanced poorly-differentiated neuroendocrine carcinomas (NECs), after the failure of at least one line of prior therapy. SECONDARY OBJECTIVES: I. To evaluate progression-free survival (PFS). II. To measure the safety and tolerability of the combination of XL184 (cabozantinib), nivolumab, and ipilimumab in patients with advanced, poorly-differentiated NECs. III. To evaluate disease control rate (DCR). IV. To measure duration of response (DOR). V. To describe the tumor molecular profile using whole exome sequencing (WES) and correlate it with treatment outcome. VI. To describe the tumor molecular profile using ribonucleic acid (RNA) sequencing (RNAseq) and correlate it with treatment outcome. EXPLORATORY OBJECTIVES: I. To measure the tumor-infiltrating CD8+ T lymphocytes in pre- and on-treatment biopsies. II. To measure tumor-infiltrating myeloid derived suppressor cells (MDSCs) in pre- and on-treatment biopsies. III. To measure tumor-infiltrating tumor-associated macrophages (TAM) in the pre and on-treatment biopsies. IV. To measure the expression of programmed death-ligand 1 (PD-L1) in tumor cells and infiltrating immune cells. OUTLINE: Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-21 of cycles 1-4 and days 1-28 of subsequent cycles, nivolumab intravenously (IV) over 30 minutes on day 1, and ipilimumab IV over 90 minutes on day 1 of cycles 1-4 only. Treatment repeats every 21 for 4 cycles then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, and then every 3 months thereafter.

Conditions

• Metastatic Large Cell Neuroendocrine Carcinoma
• Metastatic Neuroendocrine Carcinoma
• Metastatic Neuroendocrine Neoplasm
• Metastatic Small Cell Neuroendocrine Carcinoma

Interventions

Type	Name	Description
DRUG	Cabozantinib S-malate	Given PO
BIOLOGICAL	Ipilimumab	Given IV
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2020-08-06
• Primary completion: 2025-01-10
• Completion: 2026-08-19
• First posted: 2019-09-06
• Last updated: 2026-04-13
• Results posted: 2025-12-12

Locations

46 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study