Avelumab in Chemo-resistant Gestational Trophoblastic Neoplasias (TROPHIMMUN)
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|ClinicalTrials.gov Identifier: NCT03135769|
Recruitment Status : Recruiting
First Posted : May 1, 2017
Last Update Posted : September 14, 2018
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. GTN patients are commonly treated with single agent treatment (methotrexate or actinomycine-D) or polychemotherapy (first line treatment EMA-CO) according to the predicted risk of resistance to single agent treatment by FIGO score. GTN patients with resistance to these treatments are treated with another single agent drug or polychemotherapy regimens.
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 need for modern targeted agents with better benefit/toxicity profiles.
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 metastasic 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.
- The case of complete and durable response to pembrolizumab was reported in a patient with multi chemo-resistant GTN.
|Condition or disease||Intervention/treatment||Phase|
|Gestational Trophoblastic Neoplasias (GTN)||Drug: Avelumab administration at 10mg/kg||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Avelumab in Chemo-resistant Gestational Trophoblastic Neoplasias (GTN)|
|Actual Study Start Date :||February 21, 2017|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||February 2023|
Avelumab administration at 10 mg/kg every 14 days during 6 months maximum
Drug: Avelumab administration at 10mg/kg
Avelumab administration at 10 mg/kg as a 1 hour IV infusion once every 14 days during 6 months (maximum).
- The rate of patients with successful normalization of hCG assays [ Time Frame: up to 6 months ]Clinical efficacy of avelumab administration will be evaluated by the rate of patients with successful normalization of hCG assays allowing for treatment discontinuation (hCG normalization). Patients will continue on treatment until the hCG assays, measured weekly, reach the institutional normal threshold and then for 3 additional cycles.
- Resistance free survival [ Time Frame: up to 6 months ]Number of patients alive free resistance (defined as a rise ≥ 20% rise over between two assays in three consecutive weekly hCG assays or plateau ≤ 10% decrease between two assays in four consecutive weekly hCG)
- Progression free survival [ Time Frame: up to 6 months ]Number of patients alive progression free survival (defined as a rise ≥ 20% rise over between two assays in three consecutive weekly hCG assays or plateau ≤ 10% decrease between two assays in four consecutive weekly hCG)
- Overall survival [ Time Frame: up to 6 months ]Number of patients alive 1 months after the end of treatment.
- Overall response rate according to RECIST [ Time Frame: up to 6 months ]Radiological response to avelumab assessed by the overall response rate according to RECIST version 1.1 criteria and immune-related RECIST criteria assessed by imaging (TAP CT scanner and / or MRI if contraindication) after cycle 4, 8 and 12
- NCI CTCAE version 4.0 [ Time Frame: up to 7 months ]The safety of avelumab administration will be evaluated throughout the duration of treatment (6 months max) and until the end of patient follow up (1 month after treatment discontinuation) according to NCI CTCAE version 4.0
- Kinetics of hCG [ Time Frame: up to 7 months ]Modeled hCGres parameter calculated with weekly values of hCG measured during treatment days after start of Avelumab treatment.
- PD-L1 expression in tumor samples [ Time Frame: up to 7 months ]To predict the efficacy of anti-PD-L1 immunotherapy, we will quantify and characterize the intra and peritumoral immune infiltrate of GTN
- Phenotype of the intratumoral immune cell infiltrate [ Time Frame: up to 7 months ]Immunohistochemistry with anti PD-L1, anti CD3, anti CD8, anti CD4, anti CD56 (uterine NK cells), anti FoxP3 primary antibodies will be performed on serial cuts of formalin fixed and paraffin embedded specimens from patients treated with avelumab.
- Phenotype of the peritumoral immune cell infiltrate [ Time Frame: up to 7 months ]Immunohistochemistry with anti PD-L1, anti CD3, anti CD8, anti CD4, anti CD56 (uterine NK cells), anti FoxP3 primary antibodies will be performed on serial cuts of formalin fixed and paraffin embedded specimens from patients treated with avelumab.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03135769
|Contact: Benoit YOU, MD||+33 4 78 864 firstname.lastname@example.org|
|Contact: Laurent VILLENEUVE||+33 4 78 864 email@example.com|
|Institut Bergonie||Not yet recruiting|
|Bordeaux, France, 33000|
|Contact: Anne Floquet|
|Centre Francois Baclesse||Recruiting|
|Caen, France, 14000|
|Contact: Florence Joly (0)2 31 45 50 50 ext +33 firstname.lastname@example.org|
|Centre Oscar Lambret||Not yet recruiting|
|Lille, France, 59000|
|Contact: Anne LESOIN|
|Marseille, France, 13000|
|Contact: Magali PROVANSAL (0)4 91 22 33 33 ext +33 email@example.com|
|Centre Antoine Lacassagne||Not yet recruiting|
|Nice, France, 06000|
|Contact: Philippe FOLLANA|
|Aphp Hopital Tenon||Recruiting|
|Paris, France, 75020|
|Contact: Jean-Pierre LOTZ (0)1 56 01 60 58 ext +33 firstname.lastname@example.org|
|Hospices Civils de Lyon - CHLS||Recruiting|
|Pierre Bénite, France, 69495|
|Contact: Benoit YOU, MD|
|Institut Universitaire Du Cancer de Toulouse - Oncopole||Recruiting|
|Toulouse, France, 31000|
|Contact: Laurence GLADIEFF (0)5 31 15 51 01 ext +33 email@example.com|
|Principal Investigator:||Benoit YOU, MD||Hospices Civils de Lyon - Centre Hospitalier Lyon Sud - Service d'Oncologie Médicale|