A Trial of Adalimumab Combined to Chemotherapy and Radiotherapy in Patients With Anaplastic Thyroid Cancers

Study Overview
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Brief Summary
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The hypothesis is that the particular richness of ATC's microenvironment in TAMs creates a unique opportunity for using Tumor Necrosis Factor blockade during chemotherapy and radiotherapy in order to counteract tumor resistance to therapy.

Official Title
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A Phase I Trial Assessing Adalimumab (Humira®), a Tumor Necrosis Factor α Inhibitor Combined to Chemotherapy and Radiotherapy in Patients With Anaplastic Thyroid Cancers

Conditions
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Anaplastic Thyroid Cancers

Intervention / Treatment
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* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven anaplastic thyroid cancers (localized or metastatic) Life-expectancy > 12 weeks No previous treatment for anaplastic thyroid cancer excepted surgery or crizotinib Written Informed consent signed Age > 18 years WHO 0-3 Neutrophil count > 1500 /mm3, Haemoglobin > 9 gr/dL, Platelet count > 100,000/mm3 Bilirubin < 1.5 mg/dL, Transaminases < 3 N in absence of liver metastases or <5 N if presence of liver metastases, PT > 70% Creatinine clearance > 50ml/mn (calculated by the MDRD formula) Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active, must use adequate contraception, during and for at least 6 months post-treatment. Evaluable disease > 1 cm within the cervico-mediastinal field of radiotherapy according to the Response Evaluation Criteria in Solid Tumors 1.1 criteria Patient affiliated to social security regimen or beneficiary of such regimen Exclusion Criteria: Prior treatment with anthracyclines Left Ventricular Ejection Fraction (LVEF) < 50% Known allergy to Adalimumab, doxorubicin, cisplatin, carboplatin or paclitaxel Chronic or acute infection < 15 days Pregnant or breastfeeding patients Any other malignancy in the past 5 years except basal cell carcinoma and carcinoma in situ of the cervix Previous and/or active demyelinating disease, such as multiple sclerosis Prior radiotherapy to the neck Concomitant therapy with agents otherwise used in the treatment of cancer (for example methotrexate for rheumatoid arthritis) Chronic (> 3 months) treatment with oral corticosteroids or another immunosuppressant within 15 days prior registration Patients with an active bleeding diathesis or taking an oral vitamin K antagonist (except low-dose Coumadin (warfarin sodium)) Other concurrent severe and/or uncontrolled disease which could compromise participation in the study (i.e. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmia, active ischemic heart disease, myocardial infarction during the previous six months, chronic liver or renal disease, active upper GI tract ulceration) Patient already enrolled in another therapeutic trial involving an investigational substance, and when such a substance has been taken during the previous 4 weeks Chronic Hepatitis B virus and previous viral hepatitis with risk of reactivation, Hepatitis C virus and human immunodeficiency virus 1 or human immunodeficiency virus 2 infection, active or latent tuberculosis infection Persons deprived of their freedom or under guardianship, or for whom it would be impossible to undergo the medical follow-up required by the trial, for geographic, social or psychological reasons Refusal or absence of biopsy (excepted for initial pathological diagnosis) will not constitute an exclusion criterion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>Adalimumab will be administrated subcutaneously 1h prior to chemotherapy at D1W1, D1W3, D1W5, D1W7, and D1W9, starting with the chemotherapy for a total duration of 9 weeks (5 injections in total) | Drug: Adalimumab<br> <br> * Other names: Humira®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended dose | Two dose levels will be investigated : Level 1: 20 mg at D1W1, D1W3, D1W5, D1W7 and D1W9. Level 2: 40 mg at D1W1, D1W3, D1W5, D1W7 and D1W9. | Up to 9 weeks |