GastroEsophageal Cancer Clinical Trial
Official title:
Phase I/II Trial of Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Cancer
Verified date | March 2022 |
Source | University of Wisconsin, Madison |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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
Status | Active, not recruiting |
Enrollment | 22 |
Est. completion date | March 2023 |
Est. primary completion date | January 19, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin |
Lead Sponsor | Collaborator |
---|---|
University of Wisconsin, Madison |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Part 1: Dose Limiting Toxicity | A total number of 6 subjects will be enrolled during the run-in phase of the trial. A sample size of 6 is sufficient to estimate the true dose limiting toxicity rate of the proposed avelumab/chemoradiation therapy with adequate accuracy. Specifically, the true dose limiting toxicity rate will be estimated with a standard error of 20%. The proposed treatment combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient. | Up to 4 weeks post-resection of all 6 Part 1 subjects. | |
Primary | Part 2: Pathological complete response rate. | Pathologic compete response (pCR) is defined as an absence of any viable tumor at microscopic examination of the primary tumor and any lymph nodes sampled after surgery following neoadjuvant therapy. Participants with invalid/missing pCR assessments will be defined as non-responders. The number and frequency of patients with a pCR will be summarized in tabular format. The pCR rate will be reported along with the corresponding 90% confidence interval which will be constructed using the Wilson score method. | Post-resection (80-100 days) pathology review for all 24 Part 2 subjects. | |
Secondary | Number of Adverse Events | Part 2 will further evaluate the safety of the studied drug combination, building on the observations from Part 1.
All patients who receive at least one dose of avelumab will be evaluated for toxicity. Toxicities observed will be summarized in terms of types and severities by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. The number and severity of toxicity incidents will be analyzed descriptively in tabular format. The 90% confidence interval for the dose limiting toxicity rate (DLT) will be constructed using the Wilson score method. |
Up to 30 days post-avelumab of all 24 Part 2 subjects. | |
Secondary | Number of Subjects who Complete Planned Treatment | Part 2 will further evaluate the tolerability of the studied drug combination, building on the observations from Part 1.
Tolerability will be reported as the number of subjects who did or did not complete the planned treatment, including the reason they ended treatment early. |
Up to 30 days post-avelumab of all 24 Part 2 subjects. | |
Secondary | Disease free survival | Disease free survival (DFS) will be defined as the number of days from the day of resection to the day a subject experiences an event of disease recurrence or death, whichever comes first. If a subject has not experienced an event of disease recurrence progression or death at the time of analysis, then the subject's data will be censored at the date of the last available evaluation. DFS will be summarized using point estimates of the median time to progression and the associated 95% confidence interval. The data will be presented graphically using Kaplan-Meier plots. | Up to 4 years post-resection for all 24 subjects. | |
Secondary | Incidence of surgical complications | Incidence of surgical complications will be calculated and reported along with the corresponding 95% confidence intervals which will be constructed using the Wilson score method. | Following resection (80-100 days) for all 24 subjects. | |
Secondary | Rate of R0 resection | Rate of R0 resection will be calculated and reported along with the corresponding 95% confidence intervals which will be constructed using the Wilson score method. | Following pathology review post-resection (80-100 days) for all 24 subjects. |
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