Adjuvant Avelumab in Merkel Cell Cancer
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 with or without radiation therapy. Monoclonal antibodies, such as avelumab, may stimulate the immune system and interfere with the ability of tumor cells to grow and spread.
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
|Eligible Ages||18 Years and Over|
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 as determined by the treating investigator) - Estimated life expectancy greater than 3 years - Must start the study treatment no more than 60 days from the last dose of RT (if administered) and no more than 120 days from the date of surgical removal of nodal metastases - 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: 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 - (NOTE: Patients presenting with nodal metastases in one lymph node basin and no known primary tumor are allowed to enroll) - 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 [CTCAE] version [v] 4.0) 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, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 grade >= 3) that could interfere with study endpoints or put patient safety at risk - Pregnant or breast-feeding women
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 0: Exploratory study involving very limited human exposure to the drug to determine whether a drug is modulating its target.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|University of Washington|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Stage III Merkel Cell Carcinoma AJCC v7, Stage IIIB Merkel Cell Carcinoma AJCC v7|
- 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 (surgery with/without adjuvant radiation therapy [RT]).
- I. To examine whether post-operative adjuvant therapy with avelumab improves overall survival (OS) as compared to placebo.
- II. To examine whether post-operative adjuvant therapy with avelumab improves distant metastases-free survival (DMFS) as compared to placebo.
- III. To assess whether post-operative 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.
- I. To explore predictive biomarkers in tissue and peripheral blood for immunogenicity of avelumab.
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