Avelumab in Refractory Testicular Germ Cell Cancer.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03403777
• Date of registration: 02/01/2018
• Prospective Registration: No
• Primary sponsor: National Cancer Institute, Slovakia
• Public title: Avelumab in Refractory Testicular Germ Cell Cancer.
• Scientific title: Phase II Study of Avelumab in Multiple Relapsed/Refractory Testicular Germ Cell Cancer.
• Date of first enrolment: November 15, 2017
• Target sample size: 8
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03403777
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Slovakia

Contacts

• Name: Michal Mego, prof
• Affiliation: National Cancer Institute (NCI)

Key inclusion & exclusion 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
pr


Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Neoplasms, Germ Cell and Embryonal

Gonadal Disorders

Testicular Diseases

Antineoplastic Agents

Molecular Mechanisms of Pharmacological Action

Testicular Neoplasms

Neoplasms

Intervention(s)

Drug: Avelumab

Primary Outcome(s)

To determine the efficacy (as measured by 12-week progression-free survival) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [Time Frame: 12-weeks]

Secondary Outcome(s)

To describe the favorable response rate of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [Time Frame: 4-weeks]

Progression-free survival (PFS) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [Time Frame: 12-months]

Toxic effects of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [Time Frame: 12-weeks]

Secondary ID(s)

NCISlovakia

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck KGaA, Darmstadt, Germany