Gestational trophoblastic neoplasias MedDRA version: 19.0 Level: PT Classification code 10061988 Term: Gestational trophoblastic tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Avelumab
Pharmaceutical Form: Solution for infusion
Sponsors
Hospices Civils de Lyon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Woman older than 18 years - Patients with gestational trophoblastic disease resistant to mono-chemotherapy (methotrexate and/or actinomycine-D) or polychemotherapy (such as EMA-CO; EMA-EP; BEP; … regimens). - No limitation in the number of previous chemotherapy lines - Patients with Eastern Cooperative Oncology Group (ECOG) performance status = 2 - Archival tumor tissue available and assessable for planned analyses, or tumor lesion biopsy feasible - Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment as defined below *Absolute granulocyte count = 1.5 x 10 9 /L *Platelet count = 100 x 10 9 /L * Haemoglobin = 9.0 g/dL (may have been blood transfused) - Patients with adequate renal function : * Calculated creatinine clearance = 30 ml/min according to the Cockcroft-Gault formula (or local institutional standard method) - Patients with adequate hepatic function *Serum bilirubin = 1.5 x UNL and AST/ALT = 2.5 X UNL (= 5 X UNL for patients with liver metastases) - Patients must have a life expectancy = 16 weeks - Confirmation by a gynecologist of non-childbearing status for women of childbearing potential Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxicT lymphocyte-associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways). - Illness, incompatible with avelumab, such as congestive heart failure; respiratory distress; liver failure; allergy. - 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. - All subjects with brain metastases, except those meeting the following criteria: o Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment, o 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). o Subjects with brain metastases must be either off steroids except a stable or decreasing dose of =CTCAE grade 2) with the exception of alopecia and sensory neuropathy, caused by previous cancer therapy. - Treatment with other investigational agents. - Bowel occlusive syndrome or other gastro-intestinal disorder that does not allow oral medication such as malabsorption. - 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). - Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. - Active infection requiring systemic therapy. - Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive) - Administration of a live vaccine within 30 days prior to study entry. - Current or prior use of immunosuppressive medication within 7 days prior to start of study treatment. The following are exceptions to this exclusion criterion: o Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent; o Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). - Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. - Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. - Treatment with oral anticoagulant such Coumadin. - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of avelumab in terms of successful normalization of hCG in patients with GTN resistant to: - Mono-chemotherapy (methotrexate and/or actinomycine-D) in cohort A. - Polychemotherapy (e.g. EMA-CO; EMA-EP; BEP; …) in cohort B ;Secondary Objective: - To assess the efficacy of avelumab in terms of resistance free survival; progression free survival; overall survival - To assess the radiological response to avelumab in patients with GTN resistant to chemotherapy - To assess the safety of avelumab in patients with GTN resistant to chemotherapy - To obtain data on tumor pathological biomarkers (PD-L1 expression and immune infiltrate) prone to be related to treatment efficacy. ;Primary end point(s): The main endpoint of this study is the rate of patients with successful normalization of hCG allowing for treatment discontinuation (hCH normalization). ;Timepoint(s) of evaluation of this end point: Patients will continue on treatment until the hCG assays, measured weekly, reach the institutional normal threshold and then for 3 additional cycles or otherwise will be stopped in the case of resistance, defined as a rise (a > 20% rise over any two consecutive weekly assays) or a plateau (one or more of a < 10% decrease in three consecutive weekly values) in the hCG level, or unacceptable toxicity and/or death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy: resistance rate and resistance free survival; radiological response and progression free survival; overall survival - Safety throughout the study - Pharmacodynamic parameters regarding kinetics of hCG - PD-L1 expression and phenotype of the intra and peritumoral immune cell infiltrate;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
France
Contacts
Public ContactIUNG Annie
Hospices Civils de Lyon
Outcome results
None listed