Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Thyroid Carcinoma, Anaplastic

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Anaplastic Thyroid Cancer

Cabozantinib

Marcia Brose, MD, PhD

Phase II, non-randomized, open-label study to determine the efficacy of cabozantinib as a firstline treatment for patients with differentiated thyroid cancer (DTC). Subjects will receive drug at a starting dose of 60mg PO QD. Subjects can receive drug as long as they continue to derive clinical benefit or until they experience unacceptable drug-related toxicity.

A Phase II Trial of Cabozantinib for the Treatment of Radioiodine (RAI)-Refractory Differentiated Thyroid Carcinoma (DTC) in the First-line Setting

Thomas Jefferson University

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nintedanib

Protein Kinase Inhibitors

Enzyme Inhibitors

Nintedanib should be administered orally at a dose of 200 mg twice daily.

Placebo should be administered orally at a dose of 200 mg twice daily. Cross-over to nintedanib is allowed after progression.

Placebo

Martin Schlumberger, MD

For the treatment of thyroid cancer with the so called targeted therapy the angiogenesis pathway has several potential targets. The Receptors for Vascular endothelial growth factor (VEGF) and especially VEGFR-2 is considered to be crucial for the initiation of the formation as well as the maintenance of tumor vasculature.

In thyroid cancer these VEGF receptors (VEGFR-1, VEGFR-2), VEGF itself and receptors of the fibroblast growth factor (FGF) and for the platelet-derived growth factor (PDGF) are often overexpressed. Other cells as pericytes and smooth muscle cells that are also involved in tumor angiogenesis express these receptors as well.

Inhibitors of the VEGFR or PDGFR pathway have been tested in thyroid cancer with positive results. However there is no treatment that is generally considered as standard of care for patients with differentiated thyroid cancer (DTC) or medullar thyroid cancer (MTC) who have progressed on one line of therapy. The classical cytotoxic chemotherapy has not shown a clinically meaningful benefit yet.

Nintedanib is a triple angiogenesis inhibitor which inhibits receptors of VEGF, FGF and PDGF. Therefore it might act not only on endothelial cells but also on pericytes and smooth muscle cells. Nintedanib also interacts with other kinases such as RET. Because of this multi-kinase activity rationale exists to investigate the effect in MTC and DTC.

Because it targets these three major angiogenesis signaling pathways it might prevent further tumor growth and related tumor escape mechanisms. Therefore nintedanib may be active in patients who have progressed on agents that target only one pathway.

Nintedanib(BIBF1120) in Thyroid Cancer

A Phase II Study Exploring the Safety and Efficacy of Nintedanib (BIBF1120) as Second Line Therapy for Patients With Either Differentiated or Medullary Thyroid Cancer Progressing After First Line Therapy.

This study will use RECIST 1.1 to measure PFS

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

This study will use RECIST 1.1 to measure RR

This study will use RECIST 1.1 to measure duration of response

The biomarker study in this protocol is exploratory in nature.Spearman Correlation Coefficient will be computed to quantify the relationship between biomarkers and between biomarkers and clinical parameters (e.g. age). Fisher's exact test or Wilcoxon rank sum test will be used to assess the significance of these relationships.

European Organisation for Research and Treatment of Cancer - EORTC

Lenvatinib

In the randomization phase, participants will receive lenvatinib until disease progression. Participants who discontinue due to confirmed disease progression will enter Extension Phase. Participants who discontinue without confirmed disease progression will be followed for tumor assessment until confirmed disease progression or initiation of anticancer therapy, at which time the participants will enter Follow-up period of Extension Phase.

In the randomization phase, participants will receive lenvatinib matched placebo until disease progression. Participants who discontinue due to confirmed disease progression will enter Extension Phase. Participants who discontinue without confirmed disease progression will be followed for tumor assessment until confirmed disease progression or initiation of anticancer therapy, at which time the participants will enter Follow-up period of Extension Phase.

Participants will received lenvatinib 24 mg (two 10-mg capsules + one 4-mg capsule) orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor.

Participants will received lenvatinib matched placebo (two 10-mg capsules + one 4-mg capsule) orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor.

The primary purpose of this study is to compare the progression-free survival (PFS) of participants with radioiodine (131 I)-refractory differentiated thyroid cancer (DTC) and radiographic evidence of disease progression within the prior 12 months treated with lenvatinib 24 mg by continuous once daily (QD) oral dosing versus placebo.

This study will be conducted in 3 phases: a Prerandomization Phase, a Randomization Phase, and an Extension Phase. The Extension Phase will consist of the Optional Open Label (OOL) Lenvatinib Treatment Period and the Follow-up Period.

A Trial of Lenvatinib (E7080) in Radioiodine (131 I)-Refractory Differentiated Thyroid Cancer in China

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131 I-Refractory Differentiated Thyroid Cancer in China

PFS is defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurs first) as determined by blinded independent imaging review (IIR) conducted by the imaging core laboratory using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Disease progression, per RECIST v1.1, is defined as at least a 20% relative increase and 5 millimeter (mm) absolute increase in the sum of the diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started, or the appearance of 1 or more new lesions.

ORR is the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

OS is measured from the date of randomization until the date of death from any cause. Participants who are lost to follow-up and participants who are alive at the date of data cut-off will be censored at the date the participants were last known to be alive.

An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs that start/increase in severity on/after the first dose of study drug up to 30 days after the final dose of study drug. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: results in death; is life threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life function; results in a congenital anomaly/birth defect; or can be defined as any other important medical event.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase II Trial of Cabozantinib for the Treatment of Radioiodine (RAI)-Refractory Differentiated Thyroid Carcinoma (DTC) in the First-line Setting	NCT02041260	Differentiated ... Poorly Differen...	Cabozantinib	18 Years -	Thomas Jefferson University
Nintedanib(BIBF1120) in Thyroid Cancer	NCT01788982	Medullary Thyro... Differentiated ...	Nintedanib Placebo	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
A Trial of Lenvatinib (E7080) in Radioiodine (131 I)-Refractory Differentiated Thyroid Cancer in China	NCT02966093	Differentiated ...	Lenvatinib Placebo	18 Years -	Eisai Inc.

Spots Global Cancer Trial Database for differentiated thyroid cancer (dtc)