A Study Combining Eribulin Mesylate With Avelumab in Cisplatin Ineligible Metastatic Urothelial Cell Cancer Patients

Exclusion Criteria

• •Subjects meeting any of the criteria below may not participate in the study:
• •Participation in another clinical study with an investigational product within 2 weeks prior to registration.
• •Any previous treatment with a PD1 or PD-L1 inhibitor, including Avelumab.
• •Previous systemic immunotherapy. Previous use of intravesical BCG is acceptable.
• •History of another primary malignancy except for:
• •* Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence. However adequately treated prostate cancer \>3 years ago with no significant change in PSA for past 6 months can be included.
• •* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• •* Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
• •Receipt of the last dose of anti-cancer therapy for local recurrence only and not for any systemic disease (immunotherapy, endocrine therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) within14 days prior to study registration and within 6 weeks for intravesical BCG or mitomycin C .
• •Mean QT interval corrected for heart rate (QTc) ≥470 ms on electrocardiogram (ECG) using Frediricia's Correction.
• •Current or prior use of immunosuppressive medication within 28 days before study registration, with the exceptions of: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) b) systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, c) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• •Any unresolved toxicity (≥CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss). Alopecia, sensory neuropathy grade ≤ 2, or other grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• •Active or prior documented autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. NOTE: Subjects with diabetes type I, vitiligo, hypo- or hyperthyroid diseases, or psoriasis not requiring immunosuppressive systemic treatment are eligible. Patients with a history of completely resolved childhood asthma or atopy are also eligible.
• •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• •History of and/or confirmed pneumonitis.
• •History of primary immunodeficiency.
• •History of organ transplantation including allogeneic stem-cell transplant.
• •History of hypersensitivity to Avelumab or Eribulin mesylate, including known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3).
• •Uncontrolled intercurrent illness including, but not limited to:
• •* ongoing or active infection requiring systemic therapy
• •* active peptic ulcer disease or gastritis, or active bleeding diatheses,
• •* psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
• •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.
• •Any subject known to have evidence of acute or chronic hepatitis B (positive HBV surface antigen), hepatitis C (perform HCV RNA if anti-HCV antibody screening test positive), or human immunodeficiency virus (HIV). Note: testing will be performed if applicable per physician discretion.
• •Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of starting treatment with Avelumab. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• •Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control. For this study male or female patients of reproductive potential need to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 90 days after last dose of study drug.
• •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
• •Brain metastases or history of leptomeningeal carcinomatosis.
• •Subjects with uncontrolled seizures.