Clinical trial: Avelumab in Chemo-resistant Gestational Trophoblastic Neoplasias (NCT03135769)

Eligibility criteria:
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) without . limitation in the number of previous chemotherapy lines without
             limitation in the number of previous chemotherapy lines

          -  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 by a gynecologist of non-childbearing status for women of childbearing
             potential.

        An evolutive pregnancy can be ruled out in the following cases: 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.

          -  Patients who gave its written informed consent to participate to the study

          -  Patients affiliated to a social insurance regime

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

        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: Brain
             metastases that have been treated locally and are clinically stable for at least 2
             weeks prior to enrollment ; 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) ; 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 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

          -  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: Intranasal,
             inhaled, topical steroids, or local steroid injections (eg, intra-articular
             injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
             prednisone or equivalent; 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 birth control.

          -  Treatment with oral anticoagulant such Coumadin.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction