Avelumab With Chemoradiation for Stage II/III Resectable Esophageal and Gastroesophageal Cancer

• Status: Recruiting
• Trial end date: 2024-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a 2 part Phase I/II clinical trial evaluating the safety, tolerability and efficacy of avelumab in combination with chemoradiation in patients with resectable esophageal and gastroesophageal cancer.

Part 1: This is the run-in phase of the trial. This portion will determine the safety and tolerability of avelumab in combination with chemoradiotherapy in 6 patients. The proposed combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient.

Part 2: This is a Phase 2 portion of the trial, which will evaluate the efficacy of the proposed treatment regimen in patients with stage II/III resectable esophageal and gastroesophageal cancer

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Wisconsin, Madison
• Collaborator: National Cancer Institute (NCI)
• Treatments: Albumin-Bound Paclitaxel; Antibodies, Monoclonal; Avelumab; Carboplatin; Paclitaxel

Criteria

Inclusion Criteria:

1. Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus and gastroesopagus (Siewert type 1-3)

2. Locoregional disease with clinical stage of T1N1 or T2-3N0-2

3. No clinical evidence of metastatic spread. Staging should include endoscopic ultrasound and PET/CT as recommended by NCCN guidelines. PET/CT should be performed within 3 weeks of signing informed consent

4. Age 18 years or older

5. ECOG performance status 0-2

6. Subjects must be deemed to be potential surgical candidates by an evaluating surgeon

7. Adequate organ function:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

2. Hemoglobin ≥ 9 g/dL (transfusions allowed)

3. Platelets ≥ 100 x 109/L

4. AST/ALT ≤ 2.5 x ULN

5. Total serum bilirubin of ≤1.5 x institutional upper limit of normal (ULN)

6. Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula

8. 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

9. Male patients must agree to use adequate birth control during the study and up to 30 days after the last avelumab dose

10. Women who are nursing must discontinue breast-feeding prior to the enrollment in the trial

11. Patient must be able and willing to comply with study procedures as per protocol

12. 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:

1. Prior history of radiation to the mediastinum

2. Diagnosis of cervical esophageal carcinoma

3. 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)

4. 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

5. Current use of immunosuppressive medication, except for the following:

1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)

2. systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent

3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

6. Active infection requiring systemic therapy at the time of study treatment initiation

7. Prior organ transplantation including allogenic stem-cell transplantation

8. Known history of testing positive for HIV or known immunodeficiency syndrome

9. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)

10. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines

11. Major surgery within prior 4 weeks of treatment initiation (the surgical incision should be fully healed prior to all neoadjuvant treatment initiation)

12. Any prior anticancer therapy for esophageal cancer

13. 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 (NCI CTCAE v5.0 Grade ≥ 3)

14. 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

15. 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

16. Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule