Neoplasms

All Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Disease Progression

Thyroid Cancer, Papillary

Adenocarcinoma, Follicular

Carcinoma, Papillary

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

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Amino Acids

Tyrosine Kinase Inhibitors

Iodine

Cadexomer iodine

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Chelating Agents

Tyrosine

177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 60 mCi (2.22 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks

177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 90mCi (3.33 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks

177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 135 mCi (4.99 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks

radionuclide therapy using 177Lu-DOTA-EB-FAPI 60 mCi (2.22 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.

177Lu-DOTA-EB-FAPI 1 radionuclide therapy

radionuclide therapy using 177Lu-DOTA-EB-FAPI 90 mCi (3.33 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.

177Lu-DOTA-EB-FAPI 2 radionuclide therapy

radionuclide therapy using 177Lu-DOTA-EB-FAPI 135 mCi (4.99 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.

177Lu-DOTA-EB-FAPI 3 radionuclide therapy

Haojun Chen, MD, PhD

Hao Fu, MD, PhD

Increased fibroblast activation protein expression is positively correlated with the dedifferentiation and aggressiveness of thyroid cancer. Radiolabeled fibroblast activation protein inhibitor therapy, also known as radioligand therapy has become a novel treatment for patients with radioactive iodine refractory thyroid cancer and disease progression after first-line treatment. However, a major problem in the therapeutic use of 177Lu-DOTA-FAPI has been its short half-life and fast rate of clearance. This study was designed to evaluate the safety, tolerability, and maximum tolerated dose of a long-lasting radiolabeled fibroblast activation protein inhibitor 177Lu-DOTA-EB-FAPI in mRAIR-TC patients with PD after TKIs treatment.

This dose-escalation study will include a maximum of 20 mRAIR-TC subjects with progressive disease after tyrosine kinases inhibitors (TKIs) treatment, with an increased radiotracer uptake in tumors on 68Ga-FAPI-46 PET/CT. The initial dose of 177Lu-DOTA-EB-FAPI is 2.22GBq (60 mCi), and subsequent cohorts receive an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed. Treatment is planned for up to 2 cycles, and the time interval between cycles is 6 weeks. The primary endpoint assessed the safety and maximum tolerated dose of 177Lu-DOTA-EB-FAPI used for radioligand therapy in patients with advanced mRAIR-TC. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-DOTA-EB-FAPI.

Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Metastatic Radioactive Iodine Refractory Thyroid Cancer

An Open-Label, Non-Randomized, Dose Escalation, Single-Center, Investigator-Initiated Trial to Determine the Safety, Dosimetry, and Preliminary Effectiveness of 177Lu-DOTA-EB-FAPI in Metastatic Radioactive Iodine Refractory Thyroid Cancer Patients With Progressive Disease After Tyrosine Kinase Inhibitors Treatment

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. Dose-limiting toxicity was defined as any 177Lu-DOTA-EB-FAPI-related AE ≥ grade 3 (G3).

The MTD is the dose level below that which 2 out of 6 subjects in a cohort have DLT

68Ga-Fibroblast activation protein inhibitor 46 will be performed for efficacy evaluation by RECIST 1.1. Particularly, 68Ga-FAPI-46 will be performed at baseline, and 6 weeks after each treatment cycle.

Dosimetry, measured as absorbed dose in tumor and normal organs (Gy/GBq), was estimated in the first treatment cycle for each patient.

The First Affiliated Hospital of Xiamen University

Antineoplastic Agents

Lenalidomide

Maleic acid

Cediranib

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.

Cediranib Maleate

Laboratory Biomarker Analysis

Chih-Yi Liao

This partially randomized phase I/II trial studies the side effects and best dose of cediranib maleate when given together with or without lenalidomide and to see how well they work in treating patients with thyroid cancer. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of thyroid cancer by blocking blood flow to the tumor. It is not yet known whether cediranib maleate is more effective when given together with lenalidomide in treating thyroid cancer.

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of cediranib maleate (cediranib) plus lenalidomide. (Phase I) II. Determine the progression-free survival rates of single agent cediranib in patients with iodine refractory, unresectable differentiated thyroid cancer (DTC) who have evidence of disease progression within 12 months of study enrollment. (Phase II) III. Determine the progression-free survival rates of cediranib in combination with lenalidomide in patients with iodine refractory, unresectable DTC who have evidence of disease progression within 12 months of study enrollment. (Phase II) IV. Compare the progression-free survival curves of single agent cediranib to combination therapy with cediranib with lenalidomide. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the response rate of cediranib in combination with lenalidomide in patients with iodine refractory, unresectable DTC who have evidence of disease progression within 12 months of study enrollment. (Phase I) II. Determine the toxicity, duration of response, progression free survival, and overall survival in patients with DTC treated with cediranib plus lenalidomide. (Phase I) III. Determine response rates and duration of response, early tumor size changes, the toxicity, and overall survival in patients with DTC treated with cediranib or cediranib plus lenalidomide. (Phase II) IV. Determine whether the presence of v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) or V-Ki-ras2 Kirsten rat sarcoma (K-RAS) mutations in patients with DTC predict response to cediranib or cediranib plus lenalidomide. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Phase I: Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-28 and lenalidomide PO QD on days 1-21 or 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Phase II: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cediranib maleate PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive cediranib maleate PO and lenalidomide PO as in Phase I. NOTE: As of April 10, 2015, patients assigned to this arm are to discontinue lenalidomide and may continue on cediranib alone.

After completion of study treatment, patients are followed up periodically.

Phase 1 was dose finding. Phase 2 parallel group comparison.

Cediranib Maleate With or Without Lenalidomide for the Treatment of Thyroid Cancer

Phase I/II Trial of Cediranib Alone or Cediranib and Lenalidomide in Iodine 131-Refractory Differentiated Thyroid Cancer

Dose limiting toxicity was defined as any of the following occurring during the first cycle (28 days) of therapy:

Hematological toxicities:

* Any grade 4 neutropenia (ANC \< 500) lasting more than 5 days
* Any grade 4 neutropenia with concomitant fever (temperature \> 38.5)
* Any grade 4 neutropenia and sepsis or other severe infection
* Any grade 4 thrombocytopenia

Any other grade 3-4 non-hematological adverse drug reactions, except untreated nausea/vomiting, or hypersensitivity reactions.

Grade 4 hypertension

Grade 4 proteinuria Delay in the administration of a subsequent dose of cediranib and lenalidomide exceeding 2 weeks, due to an adverse drug reaction

Time from enrollment on study to disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This analysis corresponds to the planned futility analysis after 40 events.

Time from study enrollment until disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Time from randomization to death from any cause. Patients who have not died are censored as of the date last known alive.

The percent change in tumor size from baseline to the end of cycle 2 (two months). The post-treatment total sum of lengths for a patient with a new lesion at cycle 2 will be scored as 1.2\*max(pre-sum, post-sum) to ensure that the appearance of new lesions corresponds to a disease progression per Response Evaluation Criteria in Solid Tumors criteria. In the event of any early deaths prior to cycle 2, a nonparametric rank sum test will be used with deaths ranked at the extreme end of the distribution.

Thyroid stimulating hormone and thyroglobulin levels

Presence or absence of B-RAF and RAS mutations at baseline--to be correlated with response rates, progression-free survival, and overall survival.

National Cancer Institute (NCI)

Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)

Phase I Dose Level 0

Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)

Phase I Dose Level +1

Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)

Phase I Dose Level +2

Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cediranib: Given PO

Cediranib Maleate: Given PO

Laboratory Biomarker Analysis: Correlative studies

Phase II Arm A (Cediranib Maleate)

Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.

Cediranib: Given PO

Cediranib Maleate: Given PO

Laboratory Biomarker Analysis: Correlative studies

Lenalidomide: Given PO

Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Chih-Yi Liao, MD

Dose limiting toxicity was no an endpoint for the phase II study.

Dose Limiting Toxicity

Phase I study did not have a futility analysis. For phase II, one patient in Arm B was enrolled while the futility analysis was ongoing.

Progression-free Survival (Phase II Futility Analysis)

Dose Level 0

Dose Level +1

Dose Level +2

Phase II Arm B (Cediranib Maleate Plus Lenalidomide)

Progression-free Survival (Final Results After Crossover)

Objective Response Rate

Overall Survival (Final Results After Crossover)

Percent change in tumor size was not an endpoint for the phase I study.

Percent Change in Tumor Size (Phase II)

These outcomes were not assessed in the Phase I study. These data were not collected and analyzed for the phase II study because combination treatment was stopped due to reaching futility criteria at interim analysis.

Serial Measurements of Thyroid Stimulating Hormone and Thyroglobulin

Mutations were not endpoints for the phase I study. These data were not collected and analyzed in the phase II study because combination treatment was stopped due to reaching futility criteria at interim analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Metastatic Radioactive Iodine Refractory Thyroid Cancer	NCT05410821	Refractory Thyr... Refractory Thyr... Refractory Thyr... Refractory Thyr...	177Lu-DOTA-EB-F... 177Lu-DOTA-EB-F... 177Lu-DOTA-EB-F...	18 Years -	The First Affiliated Hospital of Xiamen University
Cediranib Maleate With or Without Lenalidomide for the Treatment of Thyroid Cancer	NCT01208051	Refractory Diff... Refractory Thyr... Refractory Thyr... Refractory Thyr... Unresectable Th...	Cediranib Cediranib Malea... Laboratory Biom... Lenalidomide	18 Years -	National Cancer Institute (NCI)
Cediranib Maleate With or Without Lenalidomide for the Treatment of Thyroid Cancer	NCT01208051	Refractory Diff... Refractory Thyr... Refractory Thyr... Refractory Thyr... Unresectable Th...	Cediranib Cediranib Malea... Laboratory Biom... Lenalidomide	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for refractory thyroid gland papillary carcinoma