Cancer of the Esophagus
Conditions
Keywords
esophageal cancer
Brief summary
The primary purpose of this trial is to define the maximum tolerated and/or recommended phase II dose of the combination of panitumumab, oxaliplatin and capecitabine in patients undergoing radiation therapy for carcinoma of the thoracic esophagus or gastroesophageal junction. An additional primary objective is to describe the frequency and nature of grade III/IV and grade I/II toxicities associated with this regimen. Secondary objectives include describing 1-year disease-free survival and overall survival rates as well as to estimate clinical and pathologic complete response rates associated with this regimen.
Detailed description
This study has a phase I/II design. For this study the administration of panitumumab is considered investigational. Pretreatment: Part of regular cancer care and disease staging includes Chest/Abdomen CT Scan, upper endoscopic ultrasound, PET scan, J-Tube Placement (if clinically indicated), bronchoscopy (per clinician judgment), ECG, and baseline laboratory studies. During Treatment Weeks 1-5.5 of Radiation Therapy(RT)/Chemotherapy: * RT (180 cGy/fx, Mon-Fri) days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-38. * Panitumumab (per dose level) days 1, 15, 29. * Oxaliplatin (per dose level) days 1, 8, 15, 22, 29, 36. * Capecitabine (per dose level M-F) 1-5, 8-12, 15-19, 22-26, 29-33, 36-38.
Interventions
DRUGPanitumumab
Dose per cohort level (3.6, 4.8 or 6.0 mg/kg ), given intravenously (IV) days 1, 15 and 29 of radiation.
DRUGCapecitabine
Dose per cohort level (500, 625 or 825 mg/m2) taken by mouth twice each day of radiation
DRUGOxaliplatin
Dose per cohort level (30, 40, or 50 mg/m2). Given IV one day each week during radiation
RADIATIONRadiation Therapy (RT)
Daily for 6 weeks
Sponsors
Amgen
Brian Czito
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older. * Histologically or cytologically documented squamous cell carcinoma or Siewert's classification adenocarcinoma of the esophagus or proximal stomach T1-4, N0-2, M0-1, for which bimodality treatment with chemotherapy and radiation therapy is indicated. * Measurable Disease * ECOG Performance Status 0-1 * Laboratory values must be as follows: * Absolute neutrophil count \> or = 2,000/mm3, * Platelets \> or = 100,000/mm3, * Hemoglobin \> 9.0, * Total bilirubin \<1.5 x institutional upper normal limit, * Serum creatinine \<1.5 x institutional upper normal limit, * AST or ALT \< 3x institutional upper normal limit, * Magnesium equal or higher than institutional lower limit, * Creatinine clearance Estimated \> 40 ml/min, * Calcium \> lower limit of normal. * Not pregnant or lactating. Negative pregnancy test within 72 hours prior to registration (female patients of childbearing potential). Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. * Life expectancy must be \>3 months. * No serious or poorly controlled medical or psychological conditions that could be exacerbated by the treatment or would seriously complicate compliance with the protocol. * Able to swallow capecitabine (whole or crushed tablet or liquid dispersed) or patients may have a G or J tube. * No conditions that would significantly compromise intestinal absorption of the study drugs.
Exclusion criteria
* Tumors extending above the level of the thoracic inlet or beyond 5 cm below the gastroesophageal junction. * Patients with radiographic or bronchoscopic evidence of esophageal perforation. * Patients with known evidence of brain metastases, lymphangitic lung metastases, or carcinomatous meningitis. * Dementia or significantly altered mental status * Major surgery within 4 weeks of the start of study treatment * Prior chemotherapy, radiation therapy, hormonal or biologic therapy within the past 6 months. * Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine, corticosteroids) * Currently requiring medications that may interact with the metabolism or disposition of capecitabine/5-FU: dipyridamole, folinic acid, allopurinol, trimethoprim, misonidazole, metoclopramide, flucytosine or cimetidine. * Hypersensitivity to platinum containing compounds or capecitabine or any of the excipients of this product. Prior unanticipated severe reaction to fluoropyrimidine/platinum therapy, or known sensitivity to 5-fluorouracil/platinum containing compounds. * Serious, uncontrolled, concurrent infection(s). * History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications. * Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer. * Peripheral neuropathy \> grade 1 * Any of the following within 24 weeks before randomization: clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia). * Uncontrolled gastrointestinal ulcer within 28 days of randomization * History of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan * Preexisting known bleeding diathesis or coagulopathy * Plans to continue on or use of ketoconazole, phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin or St. John's Wort, 14 days prior to randomization. * History of hypersensitivity to tetracyclines * Subject known to be human immunodeficiency virus positive * Subjects known to have chronic or active hepatitis B or C infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Panitumumab Maximum Tolerated Dose in Milligrams (mg) | 60 days |
| Number of Participants With Dose-limiting Toxicities (DLTs) | Within 30 days of the last day of radiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rates for the Patients Studied on This Protocol. | One year | Number of patients alive one year after completing study protocol treatment. |
| Pathological Complete Response Rates Associated With This Regimen. | 90 days | Absence of residual viable tumor cells at the time of surgical resection of the esophagus performed 7-9 weeks following completion of chemoradiotherapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemoradiation Panitumumab, oxiplatin, capecitabine, radiation therapy | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Chemoradiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 58.97 years STANDARD_DEVIATION 10.32 |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 9 / 29 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Within 30 days of the last day of radiation
Population: All patients who received chemoradiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoradiation | Number of Participants With Dose-limiting Toxicities (DLTs) | 2 participants |
Primary
Panitumumab Maximum Tolerated Dose in Milligrams (mg)
Time frame: 60 days
Population: Per protocol and intention to treat (ITT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoradiation | Panitumumab Maximum Tolerated Dose in Milligrams (mg) | 3.6 mg |
Secondary
Overall Survival Rates for the Patients Studied on This Protocol.
Number of patients alive one year after completing study protocol treatment.
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoradiation | Overall Survival Rates for the Patients Studied on This Protocol. | 18 participants |
Secondary
Pathological Complete Response Rates Associated With This Regimen.
Absence of residual viable tumor cells at the time of surgical resection of the esophagus performed 7-9 weeks following completion of chemoradiotherapy.
Time frame: 90 days
Population: Surgery was determined according to risk factors, patient consent and resectability.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoradiation | Pathological Complete Response Rates Associated With This Regimen. | 40 percentage of participants |