TROPHIMMUN, a phase II trial of avelumab in chemo-resistant gestational trophoblastic neoplasias (GTN)

Phase 1

• Conditions: Gestational trophoblastic neoplasias; MedDRA version: 19.0Level: PTClassification code 10061988Term: Gestational trophoblastic tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

• Registration Number: EUCTR2016-002322-37-FR
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-16
• Last Update Posted: 6 February 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: Not specified

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

-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:
oBrain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment,
oNo 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).
oSubjects 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 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:
oIntranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
oSystemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
oSteroids 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified