Pharmaco-immunological Study of Interferon-alpha and Metronomic Cyclophosphamide Association in Neuroendocrine Tumors

Study Overview
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Brief Summary
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This study will evaluate the potential immunomodulatory synergy of the association of metronomic cyclophosphamide (CMC) and interferon-alpha (IFN-alpha).

Official Title
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Pharmaco-immunological Study of Interferon-alpha and Metronomic Cyclophosphamide Association in Neuroendocrine Tumors

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Metronomic cyclophosphamide
* Drug: Interferon-alpha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: performance status ECOG-WHO ≤ 1 histologically proved neuroendocrine tumor with Ki67 < or = 10%, metastatic or locally advanced without surgery possibility at least one measurable lesion based on RECIST criteria version 1.1 signed written informed consent Exclusion Criteria: previous treatment with interferon or cyclophosphamide treatment by immunosuppressive drugs diabetes complicated by coronary artery disease or vasculopathy severe respiratory failure, chronic respiratory failure, COPD history of severe heart failure severe renal or hepatic impairment diabetes complicated with coronary artery disease or vasculopathy alcoholism unweaned uncontrolled epilepsy and/or achievement of the central nervous system functions history of severe depressive syndrome presence or history of severe psychiatric condition, particularly severe depression, suicidal thoughts or attempted suicide decompensated liver cirrhosis severe myelosuppression psoriasis and sarcoidosis active disease condition or uncontrolled infection association with the yellow fever vaccine association with phenytoin in prophylaxis hypersensitivity against interferon or cyclophosphamide prior history of other malignancy except for: basal cell carcinoma of the skin, cervical intra-epithelial neoplasia and other cancer curatively treated with no evidence of disease for at least 3 years pregnancy, breast-feeding or absence of adequate contraception for fertile patients patients under guardianship, curatorship or under the protection of justice

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metronomic cyclophosphamide and interferon-alpha<br> | Drug: Metronomic cyclophosphamide<br>* 50 mg oral tablet, one tablet per day, every day for 6 months; abort if progression or intolerance<br>* Other names: CMC;Drug: Interferon-alpha<br>* 3 months of treatment from the 4th cycle metronomic cyclophosphamide : subcutaneous injection, initial dose of 3 MIU three times a week. The dose may be adjusted as tolerated to achieve a T cell counts greater than 500 / mm3<br>* Other names: IFN-alpha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of patients with an immune response defined as Tregs lymphocytes decrease ≥ 20% in blood by the flow cytometry technique |  | at 3 months of the association CMC and Interferon-alpha |