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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02155647




Registration number
NCT02155647
Ethics application status
Date submitted
2/06/2014
Date registered
4/06/2014

Titles & IDs
Public title
Avelumab in Participants With Merkel Cell Carcinoma (JAVELIN Merkel 200)
Scientific title
A Phase II, Open-Label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab (MSB0010718C) in Subjects With Merkel Cell Carcinoma
Secondary ID [1] 0 0
2014-000445-79
Secondary ID [2] 0 0
100070-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Merkel Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab

Experimental: Part A: Avelumab - Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.

Experimental: Part B: Avelumab - Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.


Treatment: Drugs: Avelumab
Avelumab was administered at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Timepoint [1] 0 0
Up to 113 weeks
Primary outcome [2] 0 0
Part B: Durable Response Rate (DRR)
Timepoint [2] 0 0
Up to 161 weeks
Secondary outcome [1] 0 0
Part A: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Timepoint [1] 0 0
Up to 325 weeks
Secondary outcome [2] 0 0
Part A: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Timepoint [2] 0 0
Up to 325 weeks
Secondary outcome [3] 0 0
Part A: Number of Participants With Treatment-Related (TR) Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Serious TEAEs and Treatment-Related TEAEs Leading to Death
Timepoint [3] 0 0
Up to 325 weeks
Secondary outcome [4] 0 0
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)
Timepoint [4] 0 0
Up to 325 weeks
Secondary outcome [5] 0 0
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)
Timepoint [5] 0 0
Up to 325 weeks
Secondary outcome [6] 0 0
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
Timepoint [6] 0 0
Up to 325 weeks
Secondary outcome [7] 0 0
Part A: Interim Analysis: Overall Survival (OS) Time
Timepoint [7] 0 0
Up to 87 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 3 Mar 2016)
Secondary outcome [8] 0 0
Part A: Final Analysis: Overall Survival (OS) Time
Timepoint [8] 0 0
Time from first administration of trial treatment until death (Up to 325 weeks)
Secondary outcome [9] 0 0
Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months
Timepoint [9] 0 0
At Month 6 and 12
Secondary outcome [10] 0 0
Part A: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies
Timepoint [10] 0 0
Up to 80 weeks
Secondary outcome [11] 0 0
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab
Timepoint [11] 0 0
Day 1, 43, 85, 169, 253, 337 and 421
Secondary outcome [12] 0 0
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb
Timepoint [12] 0 0
Day 15, 29, 43, 57, 71, 85, 99, 169, 211, 253, 337 and 421
Secondary outcome [13] 0 0
Part B: Interim Analysis: Overall Survival (OS) Time
Timepoint [13] 0 0
Up to 161 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 2 May 2019)
Secondary outcome [14] 0 0
Part B: Final Analysis: Overall Survival (OS) Time
Timepoint [14] 0 0
Time from first administration of trial treatment until death (Up to 396 weeks)
Secondary outcome [15] 0 0
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Timepoint [15] 0 0
Up to 396 weeks
Secondary outcome [16] 0 0
Part B: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Timepoint [16] 0 0
Up to 396 weeks
Secondary outcome [17] 0 0
Part B: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Timepoint [17] 0 0
Up to 396 weeks
Secondary outcome [18] 0 0
Part B: Number of Participants With Treatment-Related (TR) Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Serious TEAEs and Treatment-Related TEAEs Leading to Death
Timepoint [18] 0 0
Up to 396 weeks
Secondary outcome [19] 0 0
Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months
Timepoint [19] 0 0
At Month 6 and 12
Secondary outcome [20] 0 0
Part B: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies
Timepoint [20] 0 0
Up to 161 weeks
Secondary outcome [21] 0 0
Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab
Timepoint [21] 0 0
At Day 1, 43 and 169
Secondary outcome [22] 0 0
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb
Timepoint [22] 0 0
Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505, Day 589, Day 673

Eligibility
Key inclusion criteria
* Signed written informed consent
* Age 18 years and above
* Histologically proven MCC
* Participants must have received at least 1 line of chemotherapy for metastatic MCC and must have progressed after the most recent line of chemotherapy
* For Part B - Participants must not have received any prior systemic treatment for metastatic MCC. Prior chemotherapy treatment in the adjuvant setting (no clinically detectable disease; no metastatic disease) is allowable if the end of treatment occurred at least 6 months prior to study start)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST Version 1.1 (including skin lesions)
* Adequate hematological, hepatic and renal function (renal function considered adequate as per protocol definition)
* Highly effective contraception for both male and female participants, if the risk of conception exists
* Fresh Biopsy or Archival Tumor Tissue
* Estimated life expectancy of more than 12 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted)
* Concurrent treatment with a non permitted drug
* Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co-regulatory targets such as 4-1BB
* Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent
* Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the participant has not fully recovered from the surgery within 4 weeks
* Concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of systemic steroids (that is, for allergic reactions or the management of immune-related adverse events [irAE]) while on study is allowed. Also, participants requiring hormone replacement with corticosteroids for adrenal insufficiency are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg or equivalent prednisone per day. Note: Participants receiving bisphosphonate or denosumab are eligible.
* Participants with active central nervous system (CNS) metastases are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy
* Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin and for Part A cervical carcinoma in situ or for Part B carcinoma in situ (skin, bladder, cervical, colorectal, breast or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer)
* Prior organ transplantation, including allogeneic stem-cell transplantation
* Part A: Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS) or any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. For Part B, known history of testing positive for HIV or known AIDS in consultation with the Medical Monitor or HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if anti- HCV antibody screening test positive).
* Active or history of any autoimmune disease (except for participants with vitiligo) or immunodeficiencies that required treatment with systemic immunosuppressive drugs
* Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to (>=) 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
* Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v 4.0; however, sensory neuropathy Grade <= 2 is acceptable 14. Pregnancy or lactation
* Known alcohol or drug abuse
* Clinically significant (that is, 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
* All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the participant's tolerance of trial treatment
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent
* Legal incapacity or limited legal capacity
* Non oncology vaccine therapies for prevention of infectious disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of trial drug administration. Vaccination while on trial is also prohibited except for administration of inactivated vaccines (for example, inactivated seasonal influenza vaccine)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Tasman Oncology Research Ltd - Southport
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [6] 0 0
St John of God Subiaco Hospital - Perth
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
- Southport
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3128 - East Melbourne
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
France
State/province [12] 0 0
Alpes Maritimes
Country [13] 0 0
France
State/province [13] 0 0
Bouches-du-Rhône
Country [14] 0 0
France
State/province [14] 0 0
Doubs
Country [15] 0 0
France
State/province [15] 0 0
Loire Atlantique
Country [16] 0 0
France
State/province [16] 0 0
Nord
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Rhone
Country [19] 0 0
France
State/province [19] 0 0
Val De Marne
Country [20] 0 0
France
State/province [20] 0 0
Bordeaux
Country [21] 0 0
France
State/province [21] 0 0
Boulogne Billancourt
Country [22] 0 0
France
State/province [22] 0 0
Chambray Les Tours
Country [23] 0 0
France
State/province [23] 0 0
Dijon
Country [24] 0 0
France
State/province [24] 0 0
Grenoble
Country [25] 0 0
France
State/province [25] 0 0
Limoges
Country [26] 0 0
Germany
State/province [26] 0 0
Baden Wuerttemberg
Country [27] 0 0
Germany
State/province [27] 0 0
Hessen
Country [28] 0 0
Germany
State/province [28] 0 0
Nordrhein Westfalen
Country [29] 0 0
Germany
State/province [29] 0 0
Sachsen
Country [30] 0 0
Germany
State/province [30] 0 0
Schleswig Holstein
Country [31] 0 0
Germany
State/province [31] 0 0
Thueringen
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Italy
State/province [33] 0 0
Torino
Country [34] 0 0
Italy
State/province [34] 0 0
Milano
Country [35] 0 0
Italy
State/province [35] 0 0
Napoli
Country [36] 0 0
Italy
State/province [36] 0 0
Padova
Country [37] 0 0
Italy
State/province [37] 0 0
Perugia
Country [38] 0 0
Italy
State/province [38] 0 0
Reggio Emilia
Country [39] 0 0
Italy
State/province [39] 0 0
Roma
Country [40] 0 0
Italy
State/province [40] 0 0
Siena
Country [41] 0 0
Japan
State/province [41] 0 0
Shizuoka-Ken
Country [42] 0 0
Japan
State/province [42] 0 0
Chuo-ku
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Available to whom?
Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://bit.ly/IPD21