AzTrials
AzTrials

Differentiated Thyroid Gland CarcinomaPhase 2NCT03914300

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

A Phase 2 study testing Biospecimen Collection, Cabozantinib S-malate and Computed Tomography in people with Differentiated Thyroid Gland Carcinoma and Follicular Variant Thyroid Gland Papillary Carcinoma, run by National Cancer Institute (NCI) at 33 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Cabozantinib S-malate and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
33 sitesUnited States
Study dates
10 Feb 2020to 17 Dec 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN); =< 3.0 x ULN for patients with Gilbert's syndrome
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN
  • Alkaline phosphatase =< 3.0 x institutional ULN; =< 5.0 x ULN with documented bone metastases
  • Creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula)
  • Serum albumin >= 2.8 g/dL
  • Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
  • Urine protein/creatinine ratio (UPCR) =< 1 mg/mg
  • Serum phosphorus, calcium, magnesium, and potassium within institutional normal limits
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) test < 1.3 x ULN
  • Patients with a history of human immunodeficiency virus (HIV) infection must be on an effective anti-retroviral regimen utilizing agents that do not strongly induce or inhibit cytochrome P450 (CYP) 3A4, and must have an undetectable viral load measured within 6 months prior to study registration
  • Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
  • The effects of XL184 (cabozantinib), nivolumab, and ipilimumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study therapy. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity: 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study therapy. Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of < 1% per year. Men who receive study therapy and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of study therapy. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception
  • WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level < 40 mIU/mL
  • WOCBP and men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 5 and 7 months, respectively, after the last dose of study therapy. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) must inform the treating physician immediately
  • Patients must be able to swallow tablets
  • Patients must be able to understand be willing to sign a written informed consent document
  • Patients with impaired decision-making capacity (IDMC) will be eligible if they have a legally authorized representative (LAR) or caregiver available to assist them

Who cannot join

  • 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:
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  • 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
  • Patients must not require concomitant treatment with oral anticoagulants (e.g., warfarin, direct thrombin, and factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). The following anticoagulants are allowed:
  • Low-dose aspirin for cardioprotection (per local applicable guidelines),
  • Low-dose low molecular weight heparins (LMWH),
  • Therapeutic doses of LMWH are allowed in patients without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before the first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
  • Patients must not require systemic corticosteroids treatment (>= 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if >= 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as is steroid pre-medication for contrast allergy
  • Patients must not have a history of severe hypersensitivity reactions to any monoclonal antibodies
  • Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
  • Patients must not require concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, or St. John's wort). Because lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list. Medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, patients will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients must not have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment within seven days prior to the first dose of study treatment
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis [DVT], pulmonary embolism [PE]) within 6 months before first dose
  • GI disorders including those associated with a high risk of perforation or fistula formation:
  • The patient has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Complete healing of an intra-abdominal abscess must be confirmed before first dose
  • Clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
  • Lesions invading or encasing any major blood vessels
  • Other clinically significant disorders that would preclude safe study participation
  • Serious non-healing wound/ulcer/bone fracture
  • Uncompensated/symptomatic hypothyroidism
  • Moderate to severe hepatic impairment (Child-Pugh B or C)
  • Patients must not have had major surgery (e.g., GI surgery or removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment and from minor surgery (e.g., simple excision or tooth extraction) at least 10 days before the first dose. Patients with clinically relevant ongoing complications from prior surgery are not eligible
  • Pregnant women are excluded from this study because XL184 (cabozantinib) has the potential for teratogenic or abortifacient effects, and the effects of nivolumab and ipilimumab on the developing fetus are not well known. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued if the mother is treated with XL184 (cabozantinib), nivolumab, or ipilimumab
  • Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including high dose systemic corticosteroids, should be excluded. These include but are not limited to: immune-related neurologic disease, such as multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, or myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, or autoimmune hepatitis. Patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, type I diabetes mellitus (DM), or endocrine deficiencies (e.g., thyroiditis) managed with replacement hormones, including physiologic corticosteroids, are eligible
  • Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication, and patients with positive serology, (e.g., antinuclear antibodies [ANA] or anti-thyroid antibodies) should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United States33 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • HaysMed

    Hays, Kansas, 67601

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University Health Truman Medical Center

    Kansas City, Missouri, 64108

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • Mercy Hospital Pittsburg

    Pittsburg, Kansas, 66762

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • University of Utah Sugarhouse Health Center

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center - McKinley Campus

    Tampa, Florida, 33612

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Kansas Health System Saint Francis Campus

    Topeka, Kansas, 66606

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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).

  1. 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.

Being tested
Biospecimen Collection, Cabozantinib S-malate, Computed Tomography, Ipilimumab, Magnetic Resonance Imaging
Medical subject headings
Thyroid Neoplasms, Adenocarcinoma, Follicular, Thyroid Cancer, Papillary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Cabozantinib S-malateDrug

    Also called BMS-907351, Cabometyx, Cometriq, XL 184

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

Study groups in NCT03914300
Study groupRoleWhat they receive
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.
Receives: Procedure: Biospecimen Collection; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 6 months after initiation of therapy

Secondary outcomes (4)

  1. Treatment Related Adverse Events (TRAEs)

    Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Treatment related adverse events that occurred in >20% of participants are reported here.

    Measured: Up to 2 years

  2. Duration of Response

    From response (PR or CR) to documented progression

    Measured: From response (PR or CR) to documented progression, assessed up to approximately 25 months

  3. Progression-free Survival

    Will be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% confidence interval (CI).

    Measured: From initiation of therapy to documented progression or death, whichever occurs first, assessed up to 2 years

  4. Overall Survival

    Will be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% CI.

    Measured: From initiation of therapy to death from any cause, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2019
  2. Study start10 Feb 2020
  3. Primary completion17 Oct 2024
  4. Study completion17 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03914300
Sponsor's protocol ID
NCI-2019-02220
Other IDs
NCI-2019-02220, OSU-19088, 10240, 10240, UM1CA186712
Status last verified
Jun 2026
First submitted
11 Apr 2019
Last updated
31 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 39133806

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Cabozantinib S-malate and Computed Tomography in people with Differentiated Thyroid Gland Carcinoma and Follicular Variant Thyroid Gland Papillary Carcinoma, run by National Cancer Institute (NCI) at 33 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: Up to 6 months after initiation of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03914300, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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