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\- Woman older than 18 years |
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Low-risk gestational trophoblastic neoplasia according to FIGO score (FIGO score 6) with indication of methotrexate as first line treatment |
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Patients with Eastern Cooperative Oncology Group (ECOG) performance status 2 |
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Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment as defined below |
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Absolute granulocyte count 1.5 x 10 9 /L |
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Platelet count 100 x 10 9 /L |
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Haemoglobin 9.0 g/dL (may have been blood transfused) |
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Patients with adequate renal function |
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Calculated creatinine clearance 30 ml/min according to the Cockcroft-Gault formula (or local institutional standard method) |
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Patients with adequate hepatic function |
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Serum bilirubin 1.5 x UNL and AST/ALT 2.5 X UNL ( 5 X UNL for patients with liver metastases) |
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Patients must have a life expectancy 16 weeks |
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Confirmation of non-childbearing status for women of childbearing potential |
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An evolutive pregnancy can be ruled out in the following cases |
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in case of a previous hysterectomy |
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if serum hCG level 2 000 IU/L and no intra or extra-uterine gestational sac is detected on pelvic ultrasound |
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if serum hCG level < 2 000 IU/L on a first measurement and serum hCG increases <100% on a second measurement performed 3 days later |
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Highly effective contraception if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential must agree to use 2 highly effective contraceptions, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 12 months after avelumab treatment |
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Patients who gave its written informed consent to participate to the study |
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Patients affiliated to a social insurance regime |
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Patient is willing and able to comply with the protocol for the duration of the treatment |
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Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- CTLA 4 antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways)
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Illness, incompatible with avelumab, such as congestive heart failure; respiratory distress; liver failure; uncontrolled epilepsy; allergy
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Patients with a known allergic hypersensitivity to methotrexate or any of the other ingredients (sodium chloride, sodium hydroxide, and hydrochloric acid if excipient)
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Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for 5 years
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All subjects with brain metastases, except those meeting the following criteria
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Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment, No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
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Subjects with brain metastases must be either off steroids except a stable or decreasing dose of <10mg daily prednisone (or equivalent)
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Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug
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Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia and sensory neuropathy, caused by previous cancer therapy
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Treatment with other investigational agents
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Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication such as malabsorption
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Stomatitis, ulcers of the oral cavity and known active gastrointestinal ulcer disease
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Clinically significant (i.e., active) and severe cardiovascular disease according to investigator opinion such as myocardial infarction (< 6 months prior to enrollment)
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Patients with immune pneumonitis, pulmonary fibrosis
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Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma Global Initiative for Asthma 2011)
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Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
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Active infection requiring systemic therapy
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Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
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Administration of a live vaccine within 30 days prior to study entry
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Current or prior use of immunosuppressive medication within 7 days prior to start of study treatment
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The following are exceptions to this exclusion criterion
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Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
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Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
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Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
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Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents
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Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid
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disease not requiring immunosuppressive treatment are eligible
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Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control
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Treatment with oral anticoagulant such Coumadin
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Alcoholism (patient interview, investigator judgment)
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Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. Torsades de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation, bradycardia defined as <50 bpm), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism
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Prior organ transplantation, including allogeneic stem cell transplantation (excluding autologous bone marrow transplant)
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Patients under guardianship
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