Adenocarcinoma of the Gastroesophageal Junction, Esophageal Adenocarcinoma, Stage IIA Esophageal Cancer, Stage IIB Esophageal Cancer
Conditions
Brief summary
This phase II trial is studying how well giving panitumumab, combination chemotherapy, and radiation therapy together before surgery works in treating patients with advanced esophageal or gastroesophageal (GE) junction cancer. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, 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. Giving monoclonal antibody therapy together with chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed description
PRIMARY OBJECTIVES: I. To determine the pathologic complete response rate of a modified FOLFOX-6 regimen (leucovorin calcium, fluorouracil, and oxaliplatin) given with panitumumab at two-week intervals x 4 cycles in combination with external beam radiation therapy for patients with locally advanced adenocarcinoma of the esophagus. SECONDARY OBJECTIVES: I. To determine the toxicities and ability to complete the planned treatment. II. To determine the achieved steady-state plasma concentrations of 5-FU (fluorouracil) and correlate these with clinical toxicity. III. To assess the potential importance of polymorphic variations in genomic deoxyribonucleic acid (DNA) of pertinent genes whose protein products are the targets of the anti-neoplastic drugs used in the clinical protocol on response and toxicity to therapy. OUTLINE: Patients receive panitumumab intravenously (IV) over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42. After completion of study treatment, patients are followed up every 3 months for 2 years and then annually thereafter.
Interventions
DRUGFluorouracil
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLeucovorin Calcium
Given IV
DRUGOxaliplatin
Given IV
BIOLOGICALPanitumumab
Given IV
OTHERPharmacological Study
Correlative studies
RADIATIONRadiation Therapy
Undergo radiation therapy
PROCEDURETherapeutic Conventional Surgery
Undergo surgical resection
Sponsors
National Cancer Institute (NCI)
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have resectable adenocarcinoma of the esophagus or GE-junction and are medically fit to undergo surgery; patients must have no evidence of distant metastasis based on imaging studies * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Absolute neutrophil count (ANC) of at least 2000 per mcL * Platelet count of at least 100,000 per mcL * Serum creatinine less than or equal to 2.0 mg/dL * Serum magnesium greater than or equal to 1.8 mg/dL * Total bilirubin less than or equal to 2.0 mg per dL * Measurable disease is not required for this study, since the primary endpoint is complete pathologic response * The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
Exclusion criteria
* Prior therapy: patients with prior history of mediastinal radiation exposure will be ineligible; patients may not have received prior chemotherapy, or antibody therapy for esophageal or GE-junction adenocarcinoma * History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy * Patients with a prior history of marked intolerance to 5-fluoropyrimidines (5-FU, floxuridine, capecitabine, 5-fluorocytosine \[flucytosine\]), since such patients may have deficiency of dihydropyrimidine dehydrogenase, which places them at risk for severe and life-threatening toxicity with 5-FU * Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, ongoing immunosuppressive therapy (except for replacement steroids), active human immunodeficiency virus (HIV) infection, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety * Clinically significant cardiac disease (including symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia) within 1 year of study enrollment * Pregnant and nursing women, or women planning to become pregnant within 6 months after the end of treatment, are excluded from this study; a negative pregnancy test will be required of women of child-bearing age within 72 hours of study enrollment; subjects (male or female) who are not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment are excluded * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan * Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years * Patients receiving an investigational agent within 30 days before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Pathological Response (pCR) Rate | Up to 8 weeks | Based on the proportion who achieve pCR based on the first 4 courses of protocol treatment. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Can Undergo Resection | 4 weeks after completion of the radiation | Restaging with repeat imaging studies will be performed. If no contraindication for surgical resection is identified, resection will be performed. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Patients were followed from time of consent until the date of first documented progession or date of death from any cause, whichever came first, assessed up to 100 months. | Descriptively summarized using the method of Kaplan-Meier. Response and disease progression were assessed using RECIST criteria version 1.1 |
| Overall Survival | From the first date of therapy until the date the patient dies, assessed up to 100 months | Descriptively summarized using the method of Kaplan-Meier. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Panitumumab, Chemotherapy, Radiation) Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Treatment (Panitumumab, Chemotherapy, Radiation) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 10 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 10 / 11 |
Outcome results
Primary
Complete Pathological Response (pCR) Rate
Based on the proportion who achieve pCR based on the first 4 courses of protocol treatment. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.
Time frame: Up to 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Panitumumab, Chemotherapy, Radiation) | Complete Pathological Response (pCR) Rate | 3 Participants |
Secondary
Number of Patients Who Can Undergo Resection
Restaging with repeat imaging studies will be performed. If no contraindication for surgical resection is identified, resection will be performed. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.
Time frame: 4 weeks after completion of the radiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Panitumumab, Chemotherapy, Radiation) | Number of Patients Who Can Undergo Resection | 11 Participants |
Other Pre-specified
Overall Survival
Descriptively summarized using the method of Kaplan-Meier.
Time frame: From the first date of therapy until the date the patient dies, assessed up to 100 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Panitumumab, Chemotherapy, Radiation) | Overall Survival | 596 days |
Other Pre-specified
Progression-free Survival
Descriptively summarized using the method of Kaplan-Meier. Response and disease progression were assessed using RECIST criteria version 1.1
Time frame: Patients were followed from time of consent until the date of first documented progession or date of death from any cause, whichever came first, assessed up to 100 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Panitumumab, Chemotherapy, Radiation) | Progression-free Survival | 409 days |