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
4 other identifiers
interventional
11
1 country
33
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Feb 2020
Longer than P75 for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 11, 2019
CompletedFirst Posted
Study publicly available on registry
April 16, 2019
CompletedStudy Start
First participant enrolled
February 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 17, 2024
CompletedResults Posted
Study results publicly available
October 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 17, 2026
ExpectedApril 13, 2026
December 1, 2025
4.7 years
April 11, 2019
September 29, 2025
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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.
Up to 6 months after initiation of therapy
Secondary Outcomes (4)
Treatment Related Adverse Events (TRAEs)
Up to 2 years
Duration of Response
From response (PR or CR) to documented progression, assessed up to approximately 25 months
Progression-free Survival
From initiation of therapy to documented progression or death, whichever occurs first, assessed up to 2 years
Overall Survival
From initiation of therapy to death from any cause, assessed up to 2 years
Other Outcomes (7)
Tumor Mutation Status
Up to 2 years
Tumor Infiltrating Lymphocyte in Biopsies
Baseline up to 12 weeks after treatment start date
T Cell Receptor Repertoire in Peripheral Blood
Baseline up to 12 weeks post treatment start date
- +4 more other outcomes
Study Arms (1)
Treatment (cabozantinib S-malate, nivolumab, ipilimumab)
EXPERIMENTALPatients receive cabozantinib S-malate PO 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 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 CT or MRI during screening, and blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Given PO
Undergo CT
Given IV
Undergo MRI
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), or Hurthle cell thyroid cancer (HTC). Follicular variant of PTC or any of the above mixed histology will be allowed, as well as tall cell, insular, or poorly-differentiated thyroid cancers. Patients with anaplastic thyroid cancers (ATC) or medullary thyroid cancers (MTC) are not eligible
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Patients must have radioactive iodine (RAI)-refractory/resistant disease as defined by one or more of the following criteria:
- One or more measurable lesions that do not demonstrate RAI uptake,
- Progressive disease (PD) (new lesion or progression of previously known lesions), as defined by RECIST v1.1, within 12 months of prior RAI therapy,
- One or more measurable lesion present after cumulative RAI dose of \> 600 mCi, or
- Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan-positive disease (SUV \>= 5 in tumor lesion)
- The patient's disease must have progressed on one line of VEGFR-targeted therapy (including, but not limited to, sorafenib, sunitinib, vandetanib, pazopanib, or lenvatinib, etc.) as defined by PD per RECIST v1.1 while receiving VEGFR-targeted therapy. Patients who have received more than one line of prior VEGFR-targeted therapy will not be eligible
- Prior external beam radiation to extra-osseous disease, systemic cytotoxic chemotherapy or BRAF- or non-VEGFR-targeted therapies will be allowed, provided that \> 4 weeks has elapsed since receiving prior treatment. Radiation to bone metastases is allowed up to 2 weeks prior to initiation of study treatment
- Patients must be \>= 18 years of age. Because no dosing or adverse event data are currently available on the use of XL184 (cabozantinib), nivolumab, or ipilimumab in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Patients must have recovered to baseline or =\< Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 1 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy
- Absolute neutrophils \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 9 g/dL
- +19 more criteria
You may not qualify if:
- Patients must not have had prior treatment with XL184 (cabozantinib), any MET-targeting tyrosine kinase inhibitor (TKI), or any MET-targeting monoclonal antibody (MetMAb), such as onartuzumab
- Patients must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways
- Patients must not have a tumor invading or encasing any major blood vessels, and must not have evidence of tumor invading the gastrointestinal (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 XL184 (cabozantinib)
- Patients must not have a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Adjuvant hormonal therapy for history of prostate or breast cancer is allowed
- Patients must not have received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 4 weeks, or nitrosoureas/ mitomycin C within 6 weeks, before the first dose of study treatment. Patients may continue on bone-modifying agents (denosumab or bisphosphonates) with caution
- Patients must not have received radiation therapy:
- To the thoracic cavity, abdomen, or pelvis within 4 weeks before the first dose of study treatment;
- To bone metastases within 14 days before the first dose of study treatment;
- To any other sites within 4 weeks before the first dose of study treatment
- Patients must not have clinically relevant, ongoing complications from prior radiation therapy. Palliative (limited-field) radiation therapy is permitted as long as the patient does not have disease progression according to RECIST v 1.1
- Patients must not have received any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 4 weeks before the first dose of study treatment
- Patients must not have received any other type of investigational agent within 4 weeks before the first dose of study treatment
- Patients must not have a corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 msec by electrocardiogram (EKG) within 28 days before the first dose of study treatment
- Note: if a single EKG shows a QTcF with an absolute value \> 500 msec, two additional EKGs at intervals of approximately 3 min must be performed within 30 min after the initial EKG, and the average of these three consecutive results for QTcF will be used to determine eligibility
- Patients should not have known, untreated brain metastases or leptomeningeal metastases because of poor prognosis and concerns that progressive neurologic dysfunction could confound the evaluation of neurologic and other adverse events. However, patients will be eligible if metastases have been treated, and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment for metastases is complete and within 28 days prior to the first dose of study treatment
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
Mercy Hospital Pittsburg
Pittsburg, Kansas, 66762, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Utah Sugarhouse Health Center
Salt Lake City, Utah, 84106, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Related Publications (1)
Konda B, Sherman EJ, Massarelli E, Nieva J, Muzaffar J, Morris JC 3rd, Ryder M, Ho AL, Agulnik M, Wei L, Handley D, Moses C, Jacob R, Wright J, Streicher H, Carson W, Shah MH. Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2025 Feb 18;110(3):830-837. doi: 10.1210/clinem/dgae512.
PMID: 39133806DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Bhavana Konda
- Organization
- The Ohio State University Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Bhavana Konda
Ohio State University Comprehensive Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2019
First Posted
April 16, 2019
Study Start
February 10, 2020
Primary Completion
October 17, 2024
Study Completion (Estimated)
December 17, 2026
Last Updated
April 13, 2026
Results First Posted
October 31, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.