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Testicular NeoplasmsPhase 2NCT03403777

Avelumab in Refractory Testicular Germ Cell Cancer.

A Phase 2 study testing Avelumab in people with Testicular Neoplasms and Neoplasms, Germ Cell and Embryonal, run by National Cancer Institute, Slovakia at 1 site in Slovakia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a proof-of-concept study to define efficacy of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). Data suggest that PD-L1 is overexpressed in TGCTs, and PD-L1 expression is significantly higher in GCTs in comparison to normal testicular tissue.Patients with low PD-L1 expression had… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteSlovakia
Study dates
15 Nov 2017to 28 Feb 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • Men aged 18 years or older
  • ECOG performance status: 0-1
  • Histologically confirmed extracranial primary germ cell cancer, seminoma, or nonseminoma
  • Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer
  • Refractory GCTs e.g. patients relapsing after high-dose chemotherapy or for patients non fit enough for high-dose chemotherapy
Show all 17Show fewer
  • Primary mediastinal GCTs in first relapse
  • Patient's disease must not be amenable to cure with either surgery or chemotherapy in the opinion of investigator,
  • RECIST 1.1 Measurable disease
  • Adequate hematologic function defined by ANC ≥ 1500/mm3, platelet count ≥ 100 000/mm3 and hemoglobin level ≥ 9g/dl.
  • 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).
  • 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)]
  • At least 4 weeks must have elapsed since the last radiotherapy and/or chemotherapy before study entry,
  • At least 4 weeks must have elapsed since the last major surgery
  • Complete recovery from prior surgery, and/or reduction of all adverse events from previous systemic therapy or radiotherapy to grade 1,
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • 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.

Who cannot join

  • Patients who do not fit inclusion criteria
  • Other prior malignancy except successfully treated non-melanoma skin cancer
  • No prior PD-1/PD-L1 inhibitor
  • Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy
  • Female patients
  • Patients infected by the Human Immunodeficiency Virus (HIV)
Show all 30Show fewer
  • 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.
  • 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.
  • Hypersensitivity to any compound of the drug
  • Sexually active men not using highly effective birth control if their partners are women of child-bearing potential
  • 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)
  • Prior organ transplantation, including allogeneic stem cell transplantation
  • Significant acute or chronic infections including, among others:
  • 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)
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
  • Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
  • 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
  • Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation...) are acceptable
  • steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication).
  • 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)
  • Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable
  • Known alcohol or drug abuse
  • 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
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines

Trial locations and contacts

1 site in 1 country.

Slovakia1 site

  • National Cancer Institute

    Bratislava, 83310

Other trials in Slovakia

About this study

Official title: Phase II Study of Avelumab in Multiple Relapsed/Refractory Testicular Germ Cell Cancer.

This is a proof-of-concept study to define efficacy of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). Data suggest that PD-L1 is overexpressed in TGCTs, and PD-L1 expression is significantly higher in GCTs in comparison to normal testicular tissue.Patients with low PD-L1 expression had significantly better progression-free survival (hazard ratio [HR] = 0.40, 95% CI (0.16 - 1.01, p = 0.008) and overall survival (HR = 0.43, 95% CI (0.15 - 1.23, p = 0.040) compared to patients with high PD-L1 expression. These data suggest that PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1/PD-L1 signaling in GCTs.

Read the detailed description

Germ-cell tumours (GCTs) are extraordinarily chemosensitive and resemble the clinical and biological characteristics of a model for the cure of cancer. Nonetheless, a small proportion of patients do not have a durable complete remission (CR) with initial chemotherapy. Only 20-40% of them will be cured with the use of platinum-containing standard-dose or high-dose salvage chemotherapy with autologous stem cell transplantation (ASCT). Patients who fail to be cured after second-line salvage therapy have an extremely poor prognosis and long term survival had been documented in <5%. Paclitaxel plus ifosfamide and cisplatin is considered as a standard salvage chemotherapy in relapsed good prognosis GCTs, however, up to 40% of favourable prognosis patients failed to achieve durable response to this combination, and therefore new treatment strategies are warranted.

Recent data suggest that PD-L1 is overexpressed in TGCTs, including 73% seminomas and 64% non-seminomatous tumors, but none of normal testicular tissue specimens exhibited PD-L1 expression. In previous study that included 140 patients, PD-L1 was significantly higher in GCTs in comparison to normal testicular tissue (mean QS = 5.29 vs. 0.32, p < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features including ≥ 3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival (hazard ratio [HR] = 0.40, 95% CI (0.16 - 1.01, p = 0.008) and overall survival (HR = 0.43, 95% CI (0.15 - 1.23, p = 0.040) compared to patients with high PD-L1 expression (Figure 1).

These data suggest that PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1/PD-L1 signaling in GCTs and phase II study is warranted.

Being tested
Avelumab
Keywords
Multiple relapsed/refractory testicular germ cell tumors, Avelumab, Anti PD-L1
Medical subject headings
Testicular Neoplasms, Neoplasms, Germ Cell and Embryonal, Neoplasms, Testicular Diseases, Gonadal Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called Bavencio

    AVELUMAB will be administered intravenously 10mg/kg every 2 weeks.

Study groups in NCT03403777
Study groupRoleWhat they receive
AvelumabExperimentalAVELUMAB will be administered intravenously 10mg/kg every 2 weeks. Courses will be repeated every 14 days until progression or unacceptable toxicity. AVELUMAB will be administered as a 1-hour (-10 minutes / +20 minutes, i.e., 50-80 minutes) intravenous (i.v.) infusion. The dose of AVELUMAB will be calculated based on the weight of the subject determined on the day prior to or the day of each drug administration.
Receives: Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    12-week progression-free survival

    Measured: 12-weeks

Secondary outcomes (3)

  1. To describe the favorable response rate of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

    Favorable response rate - complete remission and/or partial remission with negative serum tumor markers

    Measured: 4-weeks

  2. Progression-free survival (PFS) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

    Progression-free survival (PFS) will be calculated from the beginning of the treatment until progression or death from disease-specific cause on intention-to-treat basis.

    Measured: 12-months

  3. Toxic effects of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

    Toxicity according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE)

    Measured: 12-weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2018
  2. Study start15 Nov 2017
  3. Primary completion28 Feb 2019
  4. Study completion28 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Non-randomized, open-label, multi-centre trial to assess efficacy (as measured by 12-week progression-free survival) of AVELUMAB in patients with refractory germ cell tumors (GCTs). The Simon optimal 2-stage design (see statistical section) will be used. See section 6 (Statistical Considerations) for specific details.
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03403777
Sponsor's protocol ID
NCISlovakia
Status last verified
Mar 2019
First submitted
2 Jan 2018
Last updated
5 Mar 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 1) Broun ER et al. Ann Intern Med 1993; 117: 124-8 2) Cierna et al., Ann Oncol, Ann Oncol. 2016 Feb;27(2):300-5. 3) Feldman et al Cancer 2012;118:981-6. 4) Horwich A, et al. Lancet 2006; 367: 754-65 5) Kollmannsberger C et al. Cancer 2006; 106: 1217-26 6) Kondagunta GV et al. J Clin Oncol. 2005 23:6549-55. 7) Mardiak J et al. Neoplasma, 2005; 52: 497-501 8) Fankhauser, C. D et al. Br J Cancer. 2015, 113: 411-413 9) Heery et al. J Clin Oncol 33, 2015 (suppl; abstr 3055) 10) Yamada et al. J Clin Oncol 33, 2015 (suppl; abstr 4047) 11) Disis et al. J Clin Oncol 33, 2015 (suppl; abstr 5509) 12) Gulley et al. J Clin Oncol 33, 2015 (suppl; abstr 8034) 13) Shitara K et al. J Clin Oncol 33, 2015 (suppl; abstr 3023) 14) Kelly K et al. J Clin Oncol 33, 2015 (suppl; abstr 3044) 15) Boyerinas B et al. Cancer Immunol Res. 2015 Oct;3(10):1148-57.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab in people with Testicular Neoplasms and Neoplasms, Germ Cell and Embryonal, run by National Cancer Institute, Slovakia at 1 site in Slovakia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03403777, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.

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