Low-risk gestational trophoblastic neoplasia MedDRA version: 20.0 Level: LLT Classification code 10018211 Term: Gestational trophoblastic tumor NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: avelumab
Product Name: Avelumab
Pharmaceutical Form: Solution for infusion
Trade Name: METHOTREXATE
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
Sponsors
Hospices Civils de Lyon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Woman older than 18 years - Low-risk gestational trophoblastic neoplasia according to FIGO score (FIGO score = 6) with indication of methotrexate as first line treatment - Patients with Eastern Cooperative Oncology Group (ECOG) performance status = 2 - 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 of non-childbearing status for women of childbearing potential. An evolutive pregnancy can be ruled out in the following cases: * in case of a previous hysterectomy * if serum hCG level = 2 000 IU/L and no intra or extra-uterine gestational sac is detected on pelvic ultrasound * if serum hCG level =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- 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; uncontrolled epilepsy; 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 enrolment, 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, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication such as malabsorption. - Clinically significant (i.e., active) and severe cardiovascular disease according to investigator opinion such as myocardial infarction (< 6 months prior to enrollment) - Patients with immune pneumonitis, pulmonary fibrosis - 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 birt
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -Safety run-in : to confirm the tolerability of methotrexate and avelumab in the first 6 patients (3+3) -To assess the efficacy of avelumab and methotrexate combination in low-risk GTN patients (FIGO score = 6) as first line setting in terms of hCG normalization;Secondary Objective: -To assess the rate of treatment-emergent adverse events (TEAEs) and treatment-related adverse events (AEs), treatment-related Grade = 3 AEs, and immune-related AEs, -To assess the efficacy of avelumab and methotrexate in terms of resistance-free survival in low-risk GTN patients as first line setting ; -To assess the efficacy of avelumab and methotrexate in terms of relapse free survival in low-risk GTN patients as first line setting after an initial hCG normalization that enabled study treatment discontinuation ; -To assess the efficacy of avelumab and methotrexate in terms of overall survival in low-risk GTN patients as first line setting -To obtain translational research data on the changes in phenotypes and functions of blood NK cells during treatment, on the impact of stool and vaginal microbial flora (biotope) on efficacy, and pre-malignant tissue tumor mutational bur;Primary end point(s): -Safety run-in: Nature, number and grade of adverse events assessed using NCI-CTAE v.5 criteria; dose-limiting toxicities (DLT) during the first 3 months after the start of treatment -The main endpoint of this study is the rate of patients with successful normalization of hCG allowing for treatment discontinuation (hCG normalization). Patients will continue on treatment until the weekly hCG assays 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 between two assays, observed twice on three consecutive weekly assays) or a plateau (a < 10% decrease between two assays observed three times on four consecutive weekly assays)(Figure 6) in the hCG level, or unacceptable t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To assess the occurrence of treatment-emergent adverse events (TEAEs) and treatment-related adverse events (AEs), treatment-related Grade = 3 AEs, and immune-related AEs, according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) - Resistance rate and Resistance-free survival will evaluated according to hCG level. - Relapse-free survival will be evaluated in the case of relapse requiring treatment resumption after a hCG normalization that enabled study treatment discontinuation - Overall survival - Translational research: phenotypes and functions of blood NK cells, stool and vaginal microbial flora (biotope), and pre-malignant tissue tumor mutational burden; modeled hCG kinetic parameters of interest;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