Treatment with Recombinant human Interleukin 1 receptor antagonist (Anakinra) in patients with Anaplastic Thyroid Cancer: a proof of concept study

Non-medullary thyroid carcinoma (TC) is the most common endocrine malignancy
and worldwide one of the most rapidly increasing cancer types. Anaplastic
thyroid carcinoma (ATC), is the most aggressive form of TC, with an extremely
poor prognosis with a median survival of less than 6 months and a 5 year
relative survival of less than 14%.
The locally extensive nature of ATC usually precludes patients from any
surgical options. Furthermore, lack of sodium iodine symporter (NIS) expression
in ATC renders radioactive iodine treatment ineffective. Patients with
unresectable ATC can be offered External Beam Radiation Therapy (EBRT).
However, due to rapid progression, even this local treatment is often not
feasible and patients still die early.
To improve the prognosis and morbidity of ATC patients, there is an imperative
need to explore new treatment options that on the one hand can effectively stop
the tumor growth and help reduce tumor burden in order to make room for other
local treatments such as surgery and EBRT.
One of the most promising and increasingly used therapy options in many cancers
is targeting the antitumoral immune response. Previous studies have shown that
ATCs are highly infiltrated with inflammatory cells, and this correlates with
aggressiveness of the tumor and a poor prognosis. This local inflammatory
response, and especially Interleukin 1 (IL-1) plays an important role in
carcinogenesis and tumor progression. Results from trials using IL-1 blockade
to treat other malignancies, show that IL-1 blockade reduces metastasis and
tumor load, and improves Quality of Life (QoL) and is well tolerated in humans
with little to no toxicity.
We therefore propose a proof-of-concept study to explore the therapeutic
potential of targeting this sterile inflammatory response with recombinant
human interleukin-1 receptor antagonist (rh IL-1Ra, anakinra) in patients with
ATC.

To investigate the efficacy of treatment with human recombinant IL1Ra (rhIL1Ra,
Anakinra) in patients with ATC in terms of improved health related quality of
life (HRQoL), tumor progression and Overall Survival (OS).
Secondary objectives: To investigate the effect of treatment with IL1Ra
(Anakinra) in patients with ATC in terms of safety (occurrence and severity of
adverse events), progression free survival, performance status, and (systemic)
inflammation.

Single centre, prospective interventional proof of concept study.

IL1Ra (anakinra, Kineret ©) 600 mg/d i.v. for 1 week, followed by 100 mg/d s.c.
for a total of 6 months

Anakinra has been used in other diseases for a longer time now and is well
tolerated and associated with only few side effects, which can be monitored
easily.
In this study, only a few additional study procedures will be conducted
compared to standard care. As part of standard care, patients will be admitted
to the hospital. During this stay, they will receive anakinra treatment and
some additional blood will be drawn. For the remainder of the study, some
additional blood will be drawn (max 40 ml extra per visit), questionnaires will
need to be filled out bi-weekly, and some additional imaging (total of 4 time
points) will take place. This is will not be a significant burden for
patients.
The risks of this study are minimal and thus acceptable for patients
participating in this study because it will provide them with a treatment
option which could possibly improve their symptoms and prognosis. Patients with
ATC are faced with a very poor prognosis and current treatment options such as
surgery and EBRT are not always applicable for all ATC patients because of
advanced disease, leaving them with no other treatment options and an even
worse prognosis. Treatment with anakinra could offer these patients a second
chance, possibly leading to improved QoL, reduced tumor growth and less
morbidity, and making room for surgery or EBRT again.