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Active Not RecruitingNCT03914300

Testing the Combination of Cabozantinib, Nivolumab, and Ipilimumab (CaboNivoIpi) for Advanced Differentiated Thyroid Cancer

Phase II Study of XL184 (Cabozantinib) in Combination With Nivolumab and Ipilimumab (CaboNivoIpi) in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer Whose Cancer Progressed After One Prior VEGFR-Targeted Therapy

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

Summary

This phase II trial studies how well cabozantinib, nivolumab, and ipilimumab work in treating patients with differentiated thyroid cancer that does not respond to radioactive iodine and that worsened after treatment with a drug targeting the vascular endothelial growth factor receptor (VEGFR), a protein needed to form blood vessels. 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 work better than the usual approach consisting of chemotherapy with drugs such as doxorubicin, sorafenib, and lenvatinib for this type of thyroid cancer.

Detailed description

PRIMARY OBJECTIVE: I. To assess the objective response rate, defined as the proportion of patients who have had a partial response (PR) or complete response (CR) within the first 6 months after initiation of therapy with cabozantinib S-malate (XL184 \[cabozantinib\]), nivolumab, and ipilimumab (CaboNivoIpi). SECONDARY OBJECTIVES: I. To assess duration of objective response (DOR), progression-free survival (PFS), and overall survival (OS). II. To assess tolerability and adverse events of CaboNivoIpi in patients with differentiated thyroid cancer (DTC). EXPLORATORY OBJECTIVES: I. To correlate treatment response (Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1) with tumor mutation status. II. To correlate treatment response (RECIST v1.1) with frequency of tumor infiltrating lymphocytes in biopsies taken pre-treatment and after 12 weeks of CaboNivoIpi therapy. III. To evaluate the effect of CaboNivoIpi on T cell receptor (TCR) repertoire and to identify the frequency of shared T cell clones between tumor and peripheral blood. IV. To evaluate the effect of XL184 (cabozantinib) alone and of the CaboNivoIpi combination on peripheral blood mononuclear cells (PBMCs) and to correlate their frequency with treatment response (RECIST v1.1). V. To evaluate the effect of XL184 (cabozantinib) alone and of the CaboNivoIpi combination on myeloid-derived suppressor cells (MDSCs) and to correlate their frequency with treatment response (RECIST v1.1). VI. To correlate treatment response (RECIST v1.1) with programmed cell death protein 1 (PD-1) / programmed cell death-ligand 1 (PD-L1) expression in the primary/metastatic tumor. OUTLINE: Patients receive cabozantinib S-malate orally (PO) once daily (QD) on days -14 to -1 prior to cycle 1, days 1-42 of cycles 1-4 and days 1-28 of subsequent cycles. Patients also receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, and 29 of cycles 1-4 and day 1 of subsequent cycles and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Treatment repeats every 42 days for cycles 1-4 and every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening, and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 6 weeks, and then every 12 weeks for up to 2 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo blood sample collection
DRUGCabozantinib S-malateGiven PO
PROCEDUREComputed TomographyUndergo CT
BIOLOGICALIpilimumabGiven IV
PROCEDUREMagnetic Resonance ImagingUndergo MRI
BIOLOGICALNivolumabGiven IV

Timeline

Start date
2020-02-10
Primary completion
2024-10-17
Completion
2026-12-17
First posted
2019-04-16
Last updated
2026-04-13
Results posted
2025-10-31

Locations

33 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03914300. Inclusion in this directory is not an endorsement.