Clinical trial NCT03403777 (phase 2, status: completed)
Conditions: testicular neoplasms, neoplasms, germ cell and embryonal, neoplasms, testicular diseases, gonadal disorders, antineoplastic agents, molecular mechanisms of pharmacological action
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: avelumab
SMILES: NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1
Eligibility criteria:

        Inclusion Criteria:

          1. Signed written informed consent

          2. Men aged 18 years or older

          3. ECOG performance status: 0-1

          4. Histologically confirmed extracranial primary germ cell cancer, seminoma, or
             nonseminoma

          5. Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on
             sequential measurement or biopsy-proven unresectable germ cell cancer

          6. Refractory GCTs e.g. patients relapsing after high-dose chemotherapy or for patients
             non fit enough for high-dose chemotherapy

          7. Primary mediastinal GCTs in first relapse

          8. Patient's disease must not be amenable to cure with either surgery or chemotherapy in
             the opinion of investigator,

          9. RECIST 1.1 Measurable disease

         10. Adequate hematologic function defined by ANC ≥ 1500/mm3, platelet count ≥ 100 000/mm3
             and hemoglobin level ≥ 9g/dl.

         11. Adequate liver function defined by a total bilirubin level ≤ 1.5 ULN, and ALT, AST ≤
             2.5 × ULN . or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic
             disease to the liver).

         12. Adequate renal function: measured or calculated (by Cockcroft formula) creatinine
             clearance ≥ 30 ml/min. Cockcroft formula: CLcr = [(140-age) x weight(Kg)]/[72 x creat
             (mg/dl)]

         13. At least 4 weeks must have elapsed since the last radiotherapy and/or chemotherapy
             before study entry,

         14. At least 4 weeks must have elapsed since the last major surgery

         15. Complete recovery from prior surgery, and/or reduction of all adverse events from
             previous systemic therapy or radiotherapy to grade 1,

         16. Absence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule

         17. Highly effective contraception for both male and female subjects 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 and men able to father a child must
             agree to use 2 highly effective contraception, 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 30 days after avelumab treatment.

        Exclusion Criteria:

          1. Patients who do not fit inclusion criteria

          2. Other prior malignancy except successfully treated non-melanoma skin cancer

          3. No prior PD-1/PD-L1 inhibitor

          4. Other concurrent approved or investigational anticancer treatment, including surgery,
             radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or
             immunotherapy

          5. Female patients

          6. Patients infected by the Human Immunodeficiency Virus (HIV)

          7. 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.

          8. Other significant diseases: e.g. immune colitis, inflammatory bowel disease, immune
             pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the
             past year) or active suicidal ideation or behavior; Patients with other severe acute
             or chronic medical condition, or laboratory abnormality that would impair, in the
             judgment of investigator, excess risk associated with the study participation, study
             treatment administration, or may interfere with the interpretation of study results
             and, which, in judgment of the investigator, would make the patient inappropriate for
             entry into this study.

          9. Hypersensitivity to any compound of the drug

         10. Sexually active men not using highly effective birth control if their partners are
             women of child-bearing potential

         11. 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 must be either off steroids or on a stable or decreasing dose of <10mg
                  daily prednisone (or equivalent)

         12. Prior organ transplantation, including allogeneic stem cell transplantation

         13. Significant acute or chronic infections including, among others:

         14. Active infection requiring systemic therapy

               -  Known history of testing positive test for human immunodeficiency virus (HIV) or
                  known acquired immunodeficiency syndrome (AIDS)

               -  Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV
                  antibody tested positive)

         15. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent:

               1. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease
                  not requiring immunosuppressive treatment are eligible

               2. Subjects requiring hormone replacement with corticosteroids are eligible if the
                  steroids are administered only for the purpose of hormonal replacement and at
                  doses ≤ 10 mg or 10 mg equivalent prednisone per day

               3. Administration of steroids through a route known to result in a minimal systemic
                  exposure (topical, intranasal, intro-ocular, or inhalation...) are acceptable

               4. steroids as premedication for hypersensitivity reactions (e.g. CT scan
                  premedication).

         16. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE
             v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more
             features of partially controlled asthma)

         17. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however,
             alopecia and sensory neuropathy Grade ≤ 2 is acceptable

         18. Known alcohol or drug abuse

         19. All other significant diseases (for example, inflammatory bowel disease, uncontrolled
             asthma), which, in the opinion of the Investigator, might impair the subject's
             tolerance of trial treatment

         20. Any psychiatric condition that would prohibit the understanding or rendering of
             informed consent

         21. Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines