Avelumab in Chemo-resistant Gestational Trophoblastic Neoplasias

NCT03135769 | Completed Phase 2 DMC

• 1 other identifier: 69HCL16_0123
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief 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. 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.

Conditions

Gestational Trophoblastic Neoplasias (GTN)

Keywords

avelumab; PDL1; Gestational Trophoblastic Neoplasias; GTN; Hydatiform mole; hCG

Outcome Measures

Primary Outcomes (1)

• The rate of patients with successful normalization of hCG assays

  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.

  up to 6 months

Secondary Outcomes (9)

• Resistance free survival

  up to 6 months

• Progression free survival

  up to 6 months

• Overall survival

  up to 6 months

• Overall response rate according to RECIST

  up to 6 months

• NCI CTCAE version 4.0

  up to 7 months

Study Arms (1)

Avelumab

EXPERIMENTAL

Avelumab administration at 10 mg/kg every 14 days during 6 months maximum

Drug: Avelumab administration at 10mg/kg

Interventions

Avelumab administration at 10mg/kg DRUG

Avelumab administration at 10 mg/kg as a 1 hour IV infusion once every 14 days during 6 months (maximum).

Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Woman older than 18 years - Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patients with adequate bone marrow function :
• Absolute neutrophil 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 \< 2 000 IU/L on a first measurement and serum hCG increases \<100% on a second measurement performed 3 days later
• 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 60 days after avelumab treatment.

You may not qualify if:

• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- CTLA 4 (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:
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
• No on-going 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)
• Subjects with brain metastases must be either off steroids except a stable or decreasing dose of \<10mg daily prednisone (or equivalent)
• 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.
• Persistent toxicities (\>CTCAE grade 1) with the exception of alopecia and sensory neuropathy ≤ grade 2, 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) cardiovascular disease : cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
• Patients with severe acute or chronic medical conditions including immune pneumonitis, inflammatory bowel disease, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (6)

Institut Bergonie

Bordeaux, 33000, France

Location

Centre Francois Baclesse

Caen, 14000, France

Location

Institut Paoli-Calmettes

Marseille, 13000, France

Location

Aphp Hopital Tenon

Paris, 75020, France

Location

Hospices Civils de Lyon - CHLS

Pierre-Bénite, 69495, France

Location

Institut Universitaire Du Cancer de Toulouse - Oncopole

Toulouse, 31000, France

Location

Related Publications (2)

• You B, Bolze PA, Lotz JP, Massardier J, Gladieff L, Joly F, Hajri T, Maucort-Boulch D, Bin S, Rousset P, Devouassoux-Shisheboran M, Roux A, Alves-Ferreira M, Grazziotin-Soares D, Langlois-Jacques C, Mercier C, Villeneuve L, Freyer G, Golfier F. Avelumab in Patients With Gestational Trophoblastic Tumors With Resistance to Single-Agent Chemotherapy: Cohort A of the TROPHIMMUN Phase II Trial. J Clin Oncol. 2020 Sep 20;38(27):3129-3137. doi: 10.1200/JCO.20.00803. Epub 2020 Jul 27.

  PMID: 32716740 RESULT

• You B, Bolze PA, Lotz JP, Massardier J, Gladieff L, Floquet A, Hajri T, Descargues P, Langlois-Jacques C, Bin S, Villeneuve L, Roux A, Alves-Ferreira M, Grazziotin-Soares D, Dherret G, Gerentet C, Rousset P, Freyer G, Golfier F. Avelumab in patients with gestational trophoblastic tumors with resistance to polychemotherapy: Cohort B of the TROPHIMMUN phase 2 trial. Gynecol Oncol. 2023 Jan;168:62-67. doi: 10.1016/j.ygyno.2022.11.005. Epub 2022 Nov 16.

  PMID: 36401942 RESULT

Study Officials

• Benoit YOU, MD

  Hospices Civils de Lyon - Centre Hospitalier Lyon Sud - Service d'Oncologie Médicale

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: May 1, 2017
• Study Start: February 21, 2017
• Primary Completion: December 2, 2020
• Study Completion: March 17, 2021
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)