At a glance
ClinicalIndex Comparison Record- ✓Woman older than 18 years
- ✓Low-risk gestational trophoblastic neoplasia with FIGO score ≤6 and methotrexate indicated
- ✓ECOG performance status 0-2
- ✓Life expectancy ≥16 weeks
- ✕Prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies
- ✕Conditions incompatible with avelumab (congestive heart failure, respiratory distress, liver failure, uncontrolled epilepsy, allergy)
- ✕Allergic hypersensitivity to methotrexate or excipients
- ✕Second primary cancer (except non-melanoma skin cancer, in-situ cervical cancer, or other solid tumors with ≥5 years disease-free)
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NCT04396223Phase 2RecruitingUpdate OverdueUpdated 28mo ago · Completion was 14mo agoTROPHAMET, a Phase I/II Trial of Avelumab and METhotrexate in Low-risk Gestational TROPHoblastic Neoplasias as First Line Treatment
In Brief
A Phase 2 clinical trial evaluating Avelumab Injection and Methotrexate 1 GM Injection for Gestational Trophoblastic Neoplasias (GTN). Currently recruiting, targeting 26 participants across 9 sites.
Signals
Detailed Summary
Gestational trophoblastic neoplasias (GTN) are characterized by the persistence of elevated hCG titers after complete uterine evacuation of a partial hydatidiform mole (PHM) or a complete hydatidiform mole. Low-risk GTN patients (FIGO score ≤ 6) are commonly treated with single agent treatment (methotrexate or actinomycin-D) The cure rate, assessed by hCG normalization, is obtained in 65 to 75% of patients with these agents GTN patients with resistance to these treatments are treated with another single agent drug or polychemotherapy regimens, such as EMA-CO or BEP regimen. Chemotherapy standard regimens are old and toxic for these young lady patients, with potential long term effects detrimental for further maternity and quality of life There is a strong rational for investigating the anti-PDL1 monoclonal antibody avelumab in chemoresistant GTN patients. Several elements suggest that the normal pregnancy immune tolerance is "hijacked" by GTN cell for proliferating : * Spontaneous regressions of metastastic GTN are regularly observed, thereby the role of immune system for rejecting GTN cells. * Strong and constant overexpression of PDL1 and NK cells has been found in all subtypes and settings of GTN tumors from French reference gestational trophoblastic center. * Complete and durable responses to pembrolizumab were reported in 3 patients with multi-chemoresistant GTN in United Kingdom. * Three cases of hCG normalization with avelumab in 6 patients with chemo-resistant GTN enrolled in TROPHIMMUN cohort A (resistant to a mono-chemotherapy). * Cytotoxicity of avelumab is mediated through antibody dependent cell cytotoxicity (ADCC) by NK cells.
Study Details
Timeline
Interventions
Avelumab administration at 800mg a 1 hour IV infusion once every 14 days during 4 months ½ (median)
methotrexate administration at 1mg/kg/day during 4 months ½ (median)