Neoplasms

All Conditions

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

Adenocarcinoma, Follicular

Leukemia-Lymphoma, Adult T-Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neoplasms, Squamous Cell

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Adult T-cell Leukemia/lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients 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.

Biospecimen Collection

Cabozantinib S-malate

Computed Tomography

Magnetic Resonance Imaging

Bhavana Konda

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.

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.

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

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.

Will be summarized using frequency and compared between responders and non-responders using chi-square test or Fisher's exact test, whichever is more appropriate.

Will be described graphically using boxplots or summary measures (e.g., mean and standard errors) at each time point. Will also explore how changes in these correlative markers may differ based on whether or not the patient achieved a response. To accomplish this, will utilize different plotting characters and colors for responses versus (vs.) not in the graphical analyses to help identify potential patterns, and summarize the changes quantitatively between responders and non-responders. Changes in levels will also be compared between responders and non-responders using two sample t-test or Wilcoxon test if the data is not normally distributed. Linear mixed effect models will also be used to examine the association of biomarkers over the time with the response. Potential confounders (patients' demographics and clinical characteristics) may also be included in the models.

Will be described graphically using boxplots or summary measures (e.g., mean and standard errors) at each time point. Will also explore how changes in these correlative markers may differ based on whether or not the patient achieved a response. To accomplish this, will utilize different plotting characters and colors for responses vs. not in the graphical analyses to help identify potential patterns, and summarize the changes quantitatively between responders and non-responders. Changes in levels will also be compared between responders and non-responders using two sample t-test or Wilcoxon test if the data is not normally distributed. Linear mixed effect models will also be used to examine the association of biomarkers over the time with the response. Potential confounders (patients' demographics and clinical characteristics) may also be included in the models.

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.

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.

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

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

National Cancer Institute (NCI)

Thyroid Nodule

Micronutrients

Anti-Infective Agents

Iodine

Cadexomer iodine

Anti-Infective Agents, Local

Trace Elements

Patients receive iodine-123 PO and then undergo planar imaging and a SPECT/CT scan on study.

Iodine I-123

Planar Imaging

Single Photon Emission Computed Tomography

Clinical Trials Referral Office

Jolanta M. Durski, M.D.

This phase II study evaluates radioiodine planar and SPECT/CT imaging with iodine-123 in patients with follicular thyroid nodules prior to surgery. Because biopsy alone is not sufficient to distinguish between malignant follicular thyroid nodules and benign follicular thyroid nodules, patients with follicular thyroid lesions are referred for surgery for further evaluation. A non-invasive imaging method that can accurately determine malignancy in follicular thyroid nodules would be valuable in patient management and could potentially spare patients unnecessary surgery. Planar imagine uses a gamma camera to obtain 2D images and SPECT/CT imaging is a special type of CT scan in which a small amount of a radioactive drug is injected into a vein and a scanner is used to make detailed images of areas inside the body where the radioactive material is taken up by the tumor cells. Radioiodine planar and SPECT/CT imaging may be more accurate in distinguishing between benign follicular thyroid nodules and malignant follicular thyroid nodules to help reduce the need for surgery.

PRIMARY OBJECTIVES:

I. Determine the proportion of benign nodules appearing as hot/warm on radioiodine scans (nodule uptake \>= uptake in normal thyroid tissues).

II. To identify a possible relationship between iodine-123 (I-123) uptake on planar and single-photon emission computerized tomography (SPECT)/computerized tomography (CT) images and malignancy on surgical pathology in thyroid nodules which were previously identified by fine-needle aspiration (FNA) as indeterminate follicular neoplasms.

III. Examine correlations between intensity of uptake in follicular nodules before surgery (standard uptake values \[SUV\] on the quantitative reconstructions from our Veriton SPECT/CT scanner and nodule-to-normal thyroid background ratios on planar and SPECT images) and pathology findings and determine an SUV threshold that best distinguishes between benign and malignant nodules.

IV. Compare the usefulness of conventional planar imaging versus SPECT/CT imaging for thyroid nodules, in order to inform our optimal clinical protocol.

V. Establish an imaging protocol best suited for measuring uptake in small thyroid nodules.

OUTLINE:

Patients receive iodine-123 orally (PO) and then undergo planar imaging and a SPECT/CT scan on study.

Radioiodine Planar and a SPECT/CT Imaging With Iodine-123 for Evaluation of Follicular Thyroid Nodules Prior to Surgery

Radioiodine Scanning for Pre-Surgical Evaluation of Follicular Thyroid Nodules

Adverse events will be assessed while patients are in the nuclear medicine division undergoing positron emission tomography/computed tomography imaging.

We will compare the intensity of uptake in malignant versus benign lesions.

Mayo Clinic

Hypersensitivity

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive lenvatinib PO QD for 8 weeks and up to 12 weeks in the absence of disease progression or unaccepted toxicity. Patients also receive radioactive iodine (RAI) I-131 orally as standard of care.

Taofeek K. Owonikoko, MD, PhD

This phase II trial studies how well lenvatinib works when given together with standard of care iodine I-131 in treating patients with radioactive iodine-sensitive differentiated thyroid cancer. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of lenvatinib pretreatment along with radioactive iodine (RAI) in patients with previously treated RAI sensitive thyroid cancer.

SECONDARY OBJECTIVES:

I. To demonstrate the safety of the combination of lenvatinib and RAI in patients with Iodine sensitive differentiated thyroid carcinoma (DTC).

II. To assess dynamic changes in established serum based biomarkers of DTC (thyroglobulin \[Tg\] and Tg antibody).

III. To explore the utility of protein and genetic biomarkers to predict treatment efficacy.

OUTLINE:

Patients receive lenvatinib orally (PO) once daily (QD) for 8 weeks and up to 12 weeks in the absence of disease progression or unaccepted toxicity. Patients also receive iodine I-131 PO daily as standard of care.

After completion of study treatment, patients are followed up within 6 weeks, every 3 months for 1 year, and then periodically thereafter.

Lenvatinib and Iodine Therapy in Treating Patients With Radioactive Iodine-Sensitive Differentiated Thyroid Cancer

A Phase 2 Study of Lenvatinib in Combination With Radioactive Iodine Therapy in Patients With Progressive RAI-Sensitive Differentiated Thyroid Cancer

The time-to-progression (TTP) will be the primary endpoint for study, and will be determined using all enrolled patients in accordance with the intention to treat (ITT) principle. The study is formulated to have power = 0.90 at the significance level of 0.05 to correctly detect that improvement in median time to progression from 6 moths to 12 months.

Objective response rate and disease control rate will be summarized. For the expansion cohorts, objective response rate will be presented along with 95% exact confidence intervals.

Patients will be assigned one of the following categories: complete response (CR), partial response (PR), stable disease (SD), progressive disease, non-evaluable, and disease control (CR + PR + SD). The same method of assessment and the same technique will be used to characterize each identified and reported lesion at baseline and during follow-up.

Biochemical response will be assessed using suppressed and stimulated thyroglobulin. Thyroglobulin will be checked at baseline and post RAI every 3 months for 12 months and every 4-6 months thereafter as clinically indicated. Stimulated thyroglobulin obtained at baseline, prior to RAI, at 3 months, 6 months and 12 months post RAI will be used to define biochemical response. Unstimualte Tg levels may be used if unable to obtain stimulated Tg

Biochemical response will be assessed using suppressed and stimulated thyroglobulin antibody. Thyroglobulin antibody will be checked at baseline and post RAI every 3 months for 12 months and every 4-6 months thereafter as clinically indicated. Stimulated thyroglobulin obtained at baseline, prior to RAI, at 3 months, 6 months and 12 months post RAI will be used to define biochemical response. Unstimualte Tg levels may be used if unable to obtain stimulated Tg

Eisai Inc.

Emory University

Principal Investigator

Patients receive lenvatinib PO QD for 8 weeks and up to 12 weeks in the absence of disease progression or unaccepted toxicity. Patients also receive radioactive iodine (RAI) I-131 orally as standard of care.

Lenvatinib: Given orally once daily continuously

Treatment (Lenvatinib)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Early termination of the study because of recruitment difficulties lead to insufficient data collection and analysis of primary and secondary outcome measures. Pharmaceutical company terminated study.

Dr. Taofeek Owonikoko

No data displayed because Outcome Measure has zero total participants analyzed.The study was closed for lack of feasibility due to lack of enrollment. Therefore there is no data to report.

Time To Progression

Best Objective Response

No data displayed because Outcome Measure has zero total participants analyzed.The study was closed for lack of feasibility due to lack of enrolment. Therefore there is no data to report.

Change in Thyroglobulin Levels

Change in Thyroglobulin Antibody Levels

Patients receive 24mg of lenvatinib by mouth (PO) everyday (QD) for 8 weeks and up to 12 weeks in the absence of disease progression or unaccepted toxicity. Patients also receive radioactive iodine (RAI) I-131 orally as standard of care.

Lenvatinib: Given orally once daily continuously

Overall Study

Fluorides

Protective Agents

Patients receive fluorine F18 tetrafluoroborate IV and undergo PET/CT scan on study.

Fluorine F 18 Tetrafluoroborate

Positron Emission Tomography

Survey Administration

Stephen M. Broski, M.D.

This phase II study evaluates F-18 tetrafluoroborate (18F-TFB) PET/CT scan in patients with differentiated thyroid cancer. Diagnostic imaging is necessary for planning treatment, monitoring therapy response, and identifying sites of recurrent or metastatic disease in differentiated thyroid cancer. 18F-TFB PET/CT may accurately detect recurrent and metastatic thyroid cancer lesions, with the potential to provide information for patient management that is better than the current standard of care imaging practices.

PRIMARY OBJECTIVES:

I. Evaluate fluorine F 18 tetrafluoroborate (18F-TFB) positron emission tomography (PET)/computed tomography (CT) imaging in patients with intermediate or high risk differentiated thyroid cancer (DTC) and compare to the current clinical standard.

II. Assess the impact of 18F-TFB PET/CT on clinical management.

OUTLINE:

Patients receive fluorine F 18 tetrafluoroborate intravenously (IV) and undergo PET/CT scan on study.

Evaluation of 18F-TFB PET/CT Scan in Patients With Differentiated Thyroid Cancer

Evaluation of F-18 Tetrafluoroborate (18F-TFB) PET/CT in Patients With Differentiated Thyroid Cancer

Descriptive summaries of detected lesions (presence/absence) will include counts and proportions at the patient and lesion level. Overall concordance of these measures across modalities will be estimated using Cohen's kappa with 95% confidence intervals generated by clustered bootstrapping. Per-lesion analysis of detection rates by modality will be performed using cluster-adjusted McNemar's test, accounting for the paired nature of the data (i.e., two scans) and potential within-sample correlation for patients with multiple lesions.

Conspicuities and diagnostic confidence scores for a given lesion will be averaged across readers. Descriptive summaries of these scores will include medians and interquartile ranges. Concordance of these measures across modality will be evaluated using Lin's concordance correlation coefficient with 95% confidence intervals generated by clustered bootstrapping. Differences in conspicuities and diagnostic confidence scores will be tested using cluster-adjusted Wilcoxon signed-rank tests.

Given true positive and negative lesions determined by histopathology and/or imaging, clinical and laboratory follow-up, we will estimate sensitivity, specificity, net present value, and positive predictive value on a per-lesion and patient basis for 18F TFB PET/CT and 123I single-photon emission computerized tomography/CT along with the corresponding two-sided 95% confidence intervals. The confidence intervals will be constructed using clustered bootstrapping.

The impact of PET on clinical management in DTC patients will be evaluated using descriptive statistics. Evidence of discordance among the modalities will be assessed using a McNemar- Bowker test of symmetry.

Inter-reader reproducibility will be assessed for positivity at the patient level and region level (nominal) as well as standardized uptake values (SUVs) for positive lesions (quantitative). Reproducibility will be reported using the Fleiss' Kappa test for multiple readers for positivity and Pearson intra-class correlation for SUVs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing the Combination of Cabozantinib, Nivolumab, and Ipilimumab (CaboNivoIpi) for Advanced Differentiated Thyroid Cancer	NCT03914300	Differentiated ... Follicular Vari... Poorly Differen... Refractory Diff... Refractory Thyr... Tall Cell Varia... Thyroid Gland F... Thyroid Gland O... Thyroid Gland P...	Biospecimen Col... Cabozantinib S-... Computed Tomogr... Ipilimumab Magnetic Resona... Nivolumab	18 Years -	National Cancer Institute (NCI)
Radioiodine Planar and a SPECT/CT Imaging With Iodine-123 for Evaluation of Follicular Thyroid Nodules Prior to Surgery	NCT05591092	Thyroid Gland F...	Computed Tomogr... Iodine I-123 Planar Imaging Single Photon E...	18 Years -	Mayo Clinic
Lenvatinib and Iodine Therapy in Treating Patients With Radioactive Iodine-Sensitive Differentiated Thyroid Cancer	NCT03506048	Differentiated ... Thyroid Gland F... Thyroid Gland P...	Lenvatinib	18 Years -	Emory University
Evaluation of 18F-TFB PET/CT Scan in Patients With Differentiated Thyroid Cancer	NCT05575440	Differentiated ... Thyroid Gland F... Thyroid Gland P...	Computed Tomogr... Fluorine F 18 T... Positron Emissi... Survey Administ...	18 Years -	Mayo Clinic
Evaluation of 18F-TFB PET/CT Scan in Patients With Differentiated Thyroid Cancer	NCT05575440	Differentiated ... Thyroid Gland F... Thyroid Gland P...	Computed Tomogr... Fluorine F 18 T... Positron Emissi... Survey Administ...	18 Years -	Mayo Clinic

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