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Avelumab in Subjects With Merkel Cell Carcinoma (JAVELIN Merkel 200)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by EMD Serono
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT02155647
First received: June 2, 2014
Last updated: February 27, 2017
Last verified: February 2017
  Purpose
This is a multicenter, international, single-arm, open-label, Phase 2 trial to evaluate the efficacy and safety of avelumab in subjects with metastatic Merkel cell carcinoma (MCC).

Condition Intervention Phase
Carcinoma, Merkel Cell
Drug: Avelumab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab (MSB0010718C) in Subjects With Merkel Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Part A: Confirmed Best Overall Response (BOR) [ Time Frame: Up to 3 years ]
    BOR is defined as the confirmed best response (complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) as determined by Independent Endpoint Review Committee (IERC), obtained from start of study drug until documented disease progression, assessed every 6 weeks. CR or PR must be confirmed by a subsequent tumor assessment preferably at the next scheduled 6-weekly assessment, but no sooner than 5 weeks after the initial documentation of CR or PR.

  • Part B: Durable Response [ Time Frame: Up to 5 years ]
    Durable response is defined as objective response (complete response [CR] or partial response [PR]) according to RECIST 1.1, determined by an IERC, with a duration of at least 6 months


Secondary Outcome Measures:
  • Part A: Duration of response [ Time Frame: Up to 3 years ]
    Duration of response is defined as time from first observation of response (CR or PR) until first observation of documented disease progression or death when death occurs within 12 weeks of the last tumor assessment whichever occurs first.

  • Part A: Progression-Free Survival (PFS) Time [ Time Frame: Up to 3 years ]
    PFS time is defined as the time from first administration of study drug until first observation of disease progression or death when death occurs within 12 weeks of the last tumor assessment whichever occurs first.

  • Part A: Overall Survival (OS) Time [ Time Frame: Up to 3 years ]
    OS time is defined as the time from first administration of study drug until date of death.

  • Part A: Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 [ Time Frame: Baseline up to 90 days after last dose administration ]
  • Part A: Number of subjects with anti-avelumab antibodies [ Time Frame: Up to 3 years ]
  • Part A: Concentration at the end of infusion on Day 1 [ Time Frame: Day 1 ]
  • Part A: Trough concentrations [ Time Frame: Day 15, 29, 43, 85, 127, 169 ]
  • Part B: Confirmed Best Overall Response (BOR) [ Time Frame: Up to 5 years ]
    BOR is defined as the confirmed best response (complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) as determined by Independent Endpoint Review Committee (IERC).

  • Part B: Duration of response [ Time Frame: Up to 5 years ]
    Duration of response will be according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) as determined by Independent Endpoint Review Committee (IERC).

  • Part B: Progression-Free Survival (PFS) Time [ Time Frame: Up to 5 years ]
    PFS will be according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) as determined by Independent Endpoint Review Committee (IERC).

  • Part B: Overall Survival (OS) Time [ Time Frame: Up to 5 years ]
  • Part B: Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 [ Time Frame: Baseline up to 90 days after last dose administration ]
  • Part B: Number of subjects with anti-avelumab antibodies [ Time Frame: Up to 5 years ]
  • Part B: Concentration at the end of infusion on Day 1 [ Time Frame: Day 1 ]
  • Part B: Trough concentrations [ Time Frame: Day 15, 29, 43, 85, 127, 169 ]
  • Part A: Number of Subjects With Response Status According to RECIST 1.1 as Determined by an IERC [ Time Frame: Month 6, Month 12 ]
  • Part B: Number of Subjects With Response Status According to RECIST 1.1 as Determined by an IERC [ Time Frame: Up to 5 years ]

Estimated Enrollment: 200
Study Start Date: June 2014
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avelumab Drug: Avelumab
Avelumab will be 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.
Other Names:
  • anti-PD-L1
  • MSB0010718C

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed consent
  • Age 18 years and above
  • Histologically proven MCC
  • Subjects 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 - Subjects 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 subjects, if the risk of conception exists
  • Fresh Biopsy or Archival Tumor Tissue
  • Estimated life expectancy of more than 12 weeks

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 subject 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. Note: Subjects receiving bisphosphonate or denosumab are eligible
  • Subjects with active central nervous system (CNS) metastases are excluded. Subjects 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 subjects 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 subject'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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02155647

Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

  Show 52 Study Locations
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

Publications:
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT02155647     History of Changes
Other Study ID Numbers: 100070-003
2014-000445-79 ( EudraCT Number )
Study First Received: June 2, 2014
Last Updated: February 27, 2017

Keywords provided by EMD Serono:
Carcinoma, Merkel Cell
MSB0010718C
avelumab
anti PD-L1
JAVELIN Merkel 200

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on April 28, 2017