Clinical Trials Register

Summary
EudraCT Number:	2016-004632-38
Sponsor's Protocol Code Number:	GCTSK005
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-11
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2016-004632-38

A.3

Full title of the trial

Phase II study of Avelumab in multiple relapsed/refractory testicular germ cell cancer.

Klinické skúšanie fázy II: Avelumab u pacientov s relapsom germonatívneho tumoru.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study to evaluate the effectiveness of Avelumab in subjects with relapsed/refractory testicular germ cell cancer. Subject will intravenously receive 10 mg/kg of Avelumab every two weeks until progression or unacceptable toxicity.

Klinické skúšanie hodnotiace účinnosť Avelumabu u pacientov s relapsom nádoru semenníkov. Pacienti budu vnútrožilovo dostávať Avelumab v dávke 10 mg/kg každé dva týždne až kým nebude pozorované zhoršenie ochorenia alebo neakceptovateľná toxicita.

A.3.2

Name or abbreviated title of the trial where available

GCTSK005

A.4.1

Sponsor's protocol code number

GCTSK005

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Národný onkologický ústav
B.1.3.4	Country	Slovakia
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Národný onkologický ústav
B.4.2	Country	Slovakia
B.4.1	Name of organisation providing support	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Národný onkologický ústav
B.5.2	Functional name of contact point	Jozef Valocký
B.5.3	Address:
B.5.3.1	Street Address	Klenova 1
B.5.3.2	Town/ city	Bratislava
B.5.3.3	Post code	83310
B.5.3.4	Country	Slovakia
B.5.4	Telephone number	00421259378579

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	avelumab
D.3.2	Product code	MSB0010718C
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AVELUMAB
D.3.9.1	CAS number	1537032-82-8
D.3.9.2	Current sponsor code	MSB0010718C
D.3.9.4	EV Substance Code	SUB180078
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Extracranial primary germ cell cancer, seminoma, or nonseminoma.

Extrakraniálny primárny germinatívny tumor, seminóm alebo neseminóm.

E.1.1.1

Medical condition in easily understood language

Germ cell cancer, seminoma, or nonseminoma.

Germinatívny tumor, seminóm alebo neseminóm.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061378
E.1.2	Term	Testicular germ cell cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10039956
E.1.2	Term	Seminoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10029557
E.1.2	Term	Non-seminoma testicular cancer
E.1.2	System Organ Class	100000021189

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

Stanoviť účinnosť (hodnotenú ako prežívanie 12 týždňov bez progresie) avelumabu u pacientov s viacnásobným recidívujúcim refraktérnym germinatívnym tumorom.

E.2.2

Secondary objectives of the trial

To describe the favorable response rate, time to progression and toxic effects of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs).

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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:
a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
b. 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
c. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation...) are acceptable
d. 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

E.5 End points

E.5.1

Primary end point(s)

12-week progression-free survival rate

E.5.1.1

Timepoint(s) of evaluation of this end point

after 15 subjects are enrolled, if results are favourable, after LVLP

E.5.2

Secondary end point(s)

Response rate
Median overall survival
Median progression-free survival
Toxicity
Frequency of grade III and IV adverse events
Association between clinical outcome and biomarkers

E.5.2.1

Timepoint(s) of evaluation of this end point

after 15 patients are enrolled, if results are favourable, after LVLP

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

after 15 patients are enrolled, if results are favourable LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients with complete remission will be followed without additional therapy. Patients with radiographically detectable residual mass and normal serum tumor markers will require exploratory surgery to remove any residual masses. Patients found to have viable carcinoma in completely resected masses will be managed by either immediate post-operative chemotherapy or surveillance alone with chemotherapy at relapse, according to current recommendations.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4 Investigator Network to be involved in the Trial: 2

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-05-13

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