This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.
PRIMARY OBJECTIVES: l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma. II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma. III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab. IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation. V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma. PATIENT-REPORTED QUALITY OF LIFE OBJECTIVES: I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score. II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response. III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation. IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E. V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
203
Given IV
Correlative studies
Given IV
Ancillary studies
Undergo radiation therapy
Undergo surgery
Given IV
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
The Kirklin Clinic at Acton Road
Birmingham, Alabama, United States
Providence Hospital
Mobile, Alabama, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Disease-free Survival (DFS)
A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.
Percentage of Participants With Pathologic Complete Response at Surgery
Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor.
Time frame: At the time of surgery, 5-8 weeks after completion of radiation therapy.
Overall Survival
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Frequency of Highest Grade Adverse Event Per Participant
Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment
The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer with a total score ranging from 0-68. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). A higher score indicates better QOL. Improvement is defined as an increase from the baseline score of at least 5 points.
Time frame: Baseline, 6-8 weeks after end of radiation therapy (approximately 11.5-13.5 weeks from treatment start), 1 and 2 years from treatment start
Quality-adjusted Survival
Time frame: From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
Molecular Correlates of Efficacy
Time frame: From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
Number of Participants With Any Cardiac Adverse Events Regardless of Attribution
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Anchorage Oncology Centre
Anchorage, Alaska, United States
Katmai Oncology Group
Anchorage, Alaska, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
...and 624 more locations