A Trial of Adalimumab Combined to Chemotherapy and Radiotherapy in Patients With Anaplastic Thyroid Cancers (TAM-RT)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Anaplastic Thyroid Cancers
• Intervention / Treatment: Drug: Adalimumab

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Val de Marne
    • Villejuif, Val de Marne, France, 94805
      • Gustave Roussy Cancer Campus Grand Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; 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; Other Names: Humira®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: August 3, 2015
• First Posted (Estimate): August 6, 2015

Study Record Updates

• Last Update Posted (Estimate): January 26, 2016
• Last Update Submitted That Met QC Criteria: January 25, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: 2014-002618-22; 2014/2142 (Other Identifier: CSET number)