Clinical trial NCT02516774: A Trial of Adalimumab Combined to Chemotherapy and Radiotherapy in Patients With Anaplastic Thyroid Cancers
Official title: A Phase I Trial Assessing Adalimumab (Humira®), a Tumor Necrosis Factor α Inhibitor Combined to Chemotherapy and Radiotherapy in Patients With Anaplastic Thyroid Cancers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Anaplastic Thyroid Cancers
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
First posted: 2015-08-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Pathologically proven anaplastic thyroid cancers (localized or metastatic)
2. Life-expectancy \> 12 weeks
3. No previous treatment for anaplastic thyroid cancer excepted surgery or crizotinib
4. Written Informed consent signed
5. Age \> 18 years
6. WHO 0-3
7. Neutrophil count \> 1500 /mm3, Haemoglobin \> 9 gr/dL, Platelet count \> 100,000/mm3
8. Bilirubin \< 1.5 mg/dL, Transaminases \< 3 N in absence of liver metastases or \<5 N if presence of liver metastases, PT \> 70%
9. Creatinine clearance \> 50ml/mn (calculated by the MDRD formula)
10. 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.
11. Evaluable disease \> 1 cm within the cervico-mediastinal field of radiotherapy according to the Response Evaluation Criteria in Solid Tumors 1.1 criteria
12. Patient affiliated to social security regimen or beneficiary of such regimen

Exclusion Criteria:

1. Prior treatment with anthracyclines
2. Left Ventricular Ejection Fraction (LVEF) \< 50%
3. Known allergy to Adalimumab, doxorubicin, cisplatin, carboplatin or paclitaxel
4. Chronic or acute infection \< 15 days
5. Pregnant or breastfeeding patients
6. Any other malignancy in the past 5 years except basal cell carcinoma and carcinoma in situ of the cervix
7. Previous and/or active demyelinating disease, such as multiple sclerosis
8. Prior radiotherapy to the neck
9. Concomitant therapy with agents otherwise used in the treatment of cancer (for example methotrexate for rheumatoid arthritis)
10. Chronic (\> 3 months) treatment with oral corticosteroids or another immunosuppressant within 15 days prior registration
11. Patients with an active bleeding diathesis or taking an oral vitamin K antagonist (except low-dose Coumadin (warfarin sodium))
12. 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)
13. Patient already enrolled in another therapeutic trial involving an investigational substance, and when such a substance has been taken during the previous 4 weeks
14. 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
15. 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.

Primary outcomes:
measure: Recommended dose
timeFrame: Up to 9 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus Grand Paris
state: Val de Marne
Study officials:
References: