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Adjuvant Avelumab in Merkel Cell Cancer (ADAM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03271372
Recruitment Status : Recruiting
First Posted : September 5, 2017
Last Update Posted : February 13, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
EMD Serono
Information provided by (Responsible Party):
University of Washington

Brief Summary:
This randomized phase III trial studies how well avelumab works in treating patients with Merkel cell cancer that has spread to the lymph nodes and have undergone surgery and/or radiation therapy. Monoclonal antibodies, such as avelumab, may stimulate the immune system and interfere with the ability of tumor cells to grow and spread.

Condition or disease Intervention/treatment Phase
Stage III Merkel Cell Carcinoma AJCC v8 Stage IIIB Merkel Cell Carcinoma AJCC v8 Stage IIIA Merkel Cell Carcinoma AJCC v8 Drug: Avelumab Other: Peripheral Blood Collection Other: Placebo Phase 3

Detailed Description:

PRIMARY OBJECTIVE:

I. To compare the clinical activity of adjuvant avelumab to that of placebo, as determined by relapse-free survival in subjects with clinically detected nodal metastases from Merkel cell carcinoma (MCC) after definitive therapy with surgery [with/without adjuvant radiation therapy (RT)] or primary RT alone.

SECONDARY OBJECTIVES:

I. To examine whether adjuvant therapy with avelumab improves overall survival (OS) as compared to placebo.

II. To examine whether adjuvant therapy with avelumab improves distant metastases-free survival (DMFS) as compared to placebo.

III. To assess whether adjuvant therapy with avelumab improves disease-specific survival (DSS) as compared to placebo.

IV. To assess the safety and tolerability of avelumab in the adjuvant setting.

EXPLORATORY OBJECTIVE:

I. To explore predictive biomarkers in tissue and peripheral blood for immunogenicity of avelumab.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive avelumab intravenously (IV) over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years for a minimum of 5 years from randomization.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 3 Trial of Adjuvant Avelumab (Anti-PDL-1 Antibody) in Merkel Cell Carcinoma Patients With Clinically Detected Lymph Node Metastases
Actual Study Start Date : December 19, 2017
Estimated Primary Completion Date : August 30, 2024
Estimated Study Completion Date : August 30, 2024


Arm Intervention/treatment
Experimental: Arm I (avelumab)
Patients receive avelumab IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.
Drug: Avelumab
Given IV
Other Names:
  • Bavencio
  • MSB-0010718C
  • MSB0010718C

Other: Peripheral Blood Collection
Correlative studies

Placebo Comparator: Arm II (placebo)
Patients receive placebo IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.
Other: Peripheral Blood Collection
Correlative studies

Other: Placebo
Given IV
Other Names:
  • placebo therapy
  • PLCB
  • normal saline solution




Primary Outcome Measures :
  1. Relapse-free survival [ Time Frame: From the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurs first, assessed for up to 5 years ]
    The Kaplan-Meier technique will be used to obtain estimates.


Secondary Outcome Measures :
  1. Disease-specific survival [ Time Frame: From the date of randomization and the date of death from Merkel cell carcinoma, assessed for up to 5 years ]
    Cumulative incidence estimates will be used to summarize the probabilities of disease-specific survival.

  2. Distant-metastases free survival [ Time Frame: From the date of randomization and the date of first distant metastasis or date of death (any cause), whichever occurs first, assessed for up to 5 years ]
    The Kaplan-Meier technique will be used to obtain estimates.

  3. Incidence of adverse events [ Time Frame: Throughout the duration of the treatment (up to 2 years after randomization) ]
    Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.

  4. Overall survival [ Time Frame: From the date of randomization and the date of death, assessed for up to 5 years ]
    The Kaplan-Meier technique will be used to obtain estimates.


Other Outcome Measures:
  1. AMERK serology [ Time Frame: Up to 5 years ]
    Blood test to predict recurrence in those patients who had a positive titer at baseline.

  2. Biomarker exploration in tumor and peripheral blood samples [ Time Frame: Up to 5 years ]
    Tumor and peripheral blood samples.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Histologically confirmed MCC metastases in clinically detected lymph node(s)

    • Confirmation of the MCC diagnosis in the clinically suspicious lymph node(s) is mandatory for trial participation
    • Subjects must have had clinically-detected (i.e. either palpable or radiologically abnormal) lymph nodal metastasis
    • (NOTE: In-transit metastases without regional nodal involvement could be allowed, but only after written approval of the medical monitor)
  • Must have completed definitive treatment that included surgical removal of the clinically detected MCC metastases (with/without adjuvant radiation therapy) or primary radiation therapy as determined by the treating investigator
  • Estimated life expectancy greater than 3 years
  • Must start the study treatment no more than 120 days from the start date of definitive therapy (the date of surgical removal of nodal metastases or the date of initiation of definitive radiation therapy, as applicable)
  • Eastern Co-Operative Group (Eastern Cooperative Oncology Group [ECOG]) performance score of 0 or 1
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL (may have been transfused)
  • Total bilirubin level ≤ 1.5 x the upper limit of normal (ULN) range
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x ULN
  • Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or by 24-hour urine collection for creatinine clearance or according to local institutional standard
  • Women of childbearing potential must have a negative serum or urine pregnancy test at screening
  • Both male and female subjects must be willing to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists

    * (NOTE: The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, as stipulated in national or local guidelines. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician should be informed immediately.)

  • Must have an ability to understand and the willingness to sign a written informed consent document
  • Must consent to allow the acquisition of existing formalin-fixed paraffin-embedded (FFPE) tumor tissue, either a block or unstained slides, for performance of correlative studies

Exclusion Criteria:

  • Clinical or radiologic suspicion of residual MCC at the time of enrollment
  • Suspicion or known history of distant metastatic MCC, which is not classifiable as local recurrence or regional metastasis
  • Any prior systemic therapy (e.g. adjuvant, neo-adjuvant or concurrent use of chemotherapy, immunotherapy or an investigational agent) for MCC at any time
  • Any prior intra-lesional MCC therapy within 180 days from day 1 of study treatment
  • Residual toxicity from prior therapy grade > 1 (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [NCI-CTCAE v 5.0] that could interfere with study endpoints or put patient safety at risk
  • Previous malignant disease (other than Merkel cell carcinoma) diagnosed within 3 years from day 1 of study treatment that could interfere with study endpoints or put patient safety at risk

    * (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ [skin, bladder, cervical, colorectal, breast] or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer; any other neoplasm, which is adjudged by the treating investigator to have a low risk of recurrence during the study, could be enrolled only after written approval from the medical monitor)

  • Use of any systemic immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil et cetera, ongoing or within the last 3 months prior to day 1 of treatment

    * (NOTE: Patients on physiologic dose of corticosteroids [≤ 10 mg/day of prednisone or equivalent] for long-term hormone-replacement therapy or those requiring short, intermittent courses of corticosteroids for hypersensitivity prophylaxis [such as for iodinated computed tomography (CT) contrast prophylaxis] or those using intranasal, inhaled, topical steroids, or local steroid injection [e.g., intra-articular injection] can be allowed)

  • Immunosuppressed status due to known human immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent hematological malignancy, or other comorbidities
  • Uncontrolled intercurrent illness including, but not limited to, active serious infection, active hepatitis B or hepatitis C infection, uncontrolled seizure disorder, substance abuse disorder, or psychiatric illness/social situations that would limit compliance with study requirements or would put the patient at increased risk of complications during the study period
  • 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
  • Active or history of any serious autoimmune disease, prior organ transplantation, including allogeneic stem-cell transplantation or immune-deficiencies that required treatment with systemic immunosuppressive drugs and could flare-up during study treatment

    * (NOTE: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible)

  • Other severe acute or chronic medical conditions including immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Known prior severe hypersensitivity to investigational product or any component in its formulations that could interfere with study endpoints or put patient safety at risk
  • Pregnant or breast-feeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03271372


Contacts
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Contact: Anissa Chan 206-606-1765 anissalc@seattlecca.org

Locations
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United States, California
University of California Irvine Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Parvin Keshtmand    714-509-2739    pkeshtma@hs.uci.edu   
Principal Investigator: Samuel Ejadi         
United States, Colorado
University of Colorado Cancer Center University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Sarah Dickens    720-848-0435    sarah.dickens@cuanschutz.edu   
Principal Investigator: Karl Lewis         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Lauren Malkhasyan    813-745-3922    Lauren.Malkhasyan@moffitt.org   
Principal Investigator: Andrew Brohl         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Sunandana Chandra    312-695-1300    cancertrials@northwestern.edu   
Principal Investigator: Sunandana Chandra         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Glenn Hanna    617-632-6571    glenn_hanna@dfci.harvard.edu   
Principal Investigator: Glenn Hanna         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Susan Patton    734-647-8906    supatton@med.umich.edu   
Principal Investigator: Susan Patton         
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: Marc Ernstoff    877-275-7724    AskRoswell@roswellpark.org   
Principal Investigator: Marc Ernstoff         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ciara Kelly    646-888-4312    kellyc1@mskcc.org   
Principal Investigator: Ciara Kelly         
United States, North Carolina
University of North Carolina Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Stergios Moschos    919-843-7713    stergios_moschos@med.unc.edu   
Principal Investigator: Stergios Moschos         
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Anissa Chan    206-606-1765    anissalc@seattlecca.org   
Principal Investigator: Shailender Bhatia         
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Anissa Chan    206-606-1765    anissalc@seattlecca.org   
Principal Investigator: Shailender Bhatia         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
EMD Serono
Investigators
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Principal Investigator: Shailender Bhatia Fred Hutch/University of Washington Cancer Consortium

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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03271372    
Other Study ID Numbers: 9820
NCI-2017-00998 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RG1717054 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: February 13, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Carcinoma, Merkel Cell
Carcinoma
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Adenocarcinoma
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs