Avelumab and Chemoradiation in Treating Patients with Stage II-III Esophageal Cancer That Can Be Removed by Surgery

Status: Active

Description

This phase I / II trial studies the side effects of avelumab when given together with chemoradiation in treating patients with stage II-III esophageal cancer that can be removed by surgery. Monoclonal antibodies, such as avelumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Chemotherapy with radiation therapy may kill more tumor cells. Giving avelumab and chemoradiation may work better in treating patients with esophageal cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus
  • Locoregional disease with clinical stage of T1N1 or T2-3N0-2
  • No clinical evidence of metastatic spread; staging should include endoscopic ultrasound and positron emission tomography (PET)/computed tomography (CT) as recommended by National Comprehensive Cancer Network (NCCN) guidelines; PET/CT should be performed within 3 weeks of signing informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Subjects must be deemed to be potential surgical candidates by an evaluating surgeon
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Hemoglobin >= 9 g/dL (transfusions allowed)
  • Platelets >= 100 x 10^9/L
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Total serum bilirubin of =< 1.5 x institutional upper limit of normal (ULN)
  • Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula
  • Female patients of childbearing potential must have a negative pregnancy test (urine or serum) within 21 days prior to the start of the study drug treatment and must agree to use adequate birth control if conception is possible during the study and up to 30 days after the completion of adjuvant therapy
  • Male patients must agree to use adequate birth control during the study and up to 30 days after the last avelumab dose
  • Women who are nursing must discontinue breast-feeding prior to the enrollment in the trial
  • Patient must be able and willing to comply with study procedures as per protocol
  • Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures

Exclusion Criteria

  • Prior history of radiation to the mediastinum
  • Diagnosis of cervical esophageal carcinoma
  • Other active malignancy within the last 3 years (except for non-melanoma skin cancer, a non-invasive/in situ cancer, or indolent non metastatic Gleason 6 prostate cancer)
  • Subjects with an active or known autoimmune disease; subjects with type I diabetes mellitus, hypo- or hyperthyroidism only requiring hormone replacement/suppression, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment are eligible
  • Current use of immunosuppressive medication, except for the following: * Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) * Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Active infection requiring systemic therapy at the time of study treatment initiation
  • Prior organ transplantation including allogenic stem-cell transplantation
  • Known history of testing positive for human immunodeficiency virus (HIV) or known immunodeficiency syndrome
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid [RNA] if anti-HCV antibody screening test positive)
  • Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
  • Major surgery within prior 4 weeks of treatment initiation (the surgical incision should be fully healed prior to all neoadjuvant treatment initiation)
  • Any prior anticancer therapy for esophageal cancer
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel or avelumab, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0 grade >= 3)
  • 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; patients with stable rate-controlled atrial fibrillation will be allowed to participate
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune 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
  • Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule

Locations & Contacts

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Nataliya V. Uboha
Phone: 608-265-1700
Email: nvuboha@medicine.wisc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the safety of avelumab when combined with chemoradiation in the treatment of resectable esophageal cancer. (Part I)

II. Evaluate the safety and tolerability of the studied drug combination. (Part II)

III. Study activity of avelumab in combination with neoadjuvant chemoradiation in the treatment of resectable esophageal cancer. (Part II)

OUTLINE:

Patients receive paclitaxel intravenously (IV) over 60 minutes and carboplatin IV over 30 minutes on days 1, 8, 15, 22, and 29 and undergo radiation therapy daily over 30 minutes to 1 hour for 5 days beginning on days 1, 8, 15, 22, and 29. Patients also receive avelumab IV over 60 minutes on days 29, 43, and 57 in the absence of disease progression or unacceptable toxicity. Approximately 8 weeks after chemoradiation, patients undergo surgical resection of tumor. Beginning 2-3 weeks after surgery, patients receive avelumab IV over 60 minutes on days 1, 15, 29, 43, 57, and 71 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 16 weeks for 12 months, and every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Nataliya V. Uboha

Trial IDs

Primary ID UW17106
Secondary IDs NCI-2018-00150
Clinicaltrials.gov ID NCT03490292