Esophageal Carcinoma
Conditions
Keywords
Esophageal Carcinoma, Cisplatin, Irinotecan, Radiation Therapy, 02-045
Brief summary
Patients with surgically resectable T1N1M0 or T2-4N any M0 esophageal carcinoma will receive six weeks of induction chemotherapy with weekly irinotecan and cisplatin given weeks 1, 2, 4 and 5. Patients will then receive weekly irinotecan, cisplatin, and concurrent radiotherapy with chemotherapy given once weekly, weeks 8,9,11 and 12 during the six weeks of radiotherapy. Patients will be referred for surgery 4-8 weeks after completion of chemoradiotherapy.
Interventions
DRUGCisplatin
pts will receive weekly cisplatin 30mg/m2 after hydration on weeks 8,9,11 and 12
DRUGIrinotecan
Irinotecan will be given 65 mg/m2
RADIATIONExternal Beam Radiation Therapy
will be delivered with multiple (\>2) field techniques using mega-voltage radiation therapy. pts will receive 50.4 Gy and will be treated over a 6 week period.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be able to sign the informed consent document.
Exclusion criteria
* Tis (in-situ carcinoma) and tumors determined to be TIN0 following endoscopy, endoscopic ultrasound, or CT scanning. * Cervical esophageal tumors, * Gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus. * Prior chemotherapy or radiation. * Patients with evidence of metastatic disease are not eligible. This includes: * Positive malignant cytology of the pleura, pericardium or peritoneum. * Radiographic evidence of distant organ involvement including lung, liver, bone, or brain. * Patients with involvement of non-regional lymph nodes including supraclavicular or celiac lymph node metastases. * Biopsy proven tumor invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. Recurrent laryngeal nerve or phrenic nerve paralysis, * New York Heart Association Class III or 1V heart disease. Angina or myocardial infarction within the last 6 months, history of significant ventricular arrhythmia requiring medication with antiarrhythmics, or a history of a clinically significant conduction system abnormality. * Severe co-morbid conditions including severe uncontrolled diabetes, uncontrolled hypertension, cerebral vascular disease, uncontrolled infection, or nonmalignant illness whose control may be jeopardized by the complications of this study treatment. * Pregnant or lactating women are ineligible as the effect of the drugs used in this study on a fetus or newborn child are unknown. Premenopausal fertile females require a negative pregnancy test prior to study entry. Treatment may not begin until the results of the pregnancy tests are ascertained. Both sexes must use contraception while on this study. * History of prior malignancy (other than basal cell/squamous carcinoma of the skin, in-situ cervical carcinoma, or superficial transitional cell bladder carcinoma) diagnosed and/or treated within three years of entrance into this study. * Patients with known Gilbert's Disease. * Clinically significant hearing loss. * Serum calcium\_\>12 mg/dl. * Patients with a history of seizure disorder who are receiving phenytoin, phenobarbital, or other antiepileptic medication. * Patients who cannot fully comprehend the therapeutic implications of the protocol or comply with the requirements. * Patients with any other concurrent medical or psychiatric condition or disease, which, in the investigator's judgment, would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response | 2 years | Pathological information will be available for all patients who receive surgery. If a patient is deemed unresectable based on clinical and radiological examination after the therapy, that patient will be counted as non-responder. The best overall response is the best response recorded from the start of treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The subject's best response assignment will depend on the achievement of both measurement and confirmation criteria. We will also estimate the pathological complete response rates separately for each of these tumor types. Survival and disease-free survival will be estimated using Kaplan-Meier method. With an accrual rate of 3 patients a month, we expect the study to be completed in 18 months. |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate Toxicity and Tolerability Including Surgical Morbidity and Mortality | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combined Modality Therapy for Esophageal Carcinoma The trial will be a phase II, single institution trial of preoperative therapy with irinotecan, cisplatin, and concurrent radiotherapy in surgically resectable esophageal cancer. The primary endpoint is the pathologic complete response rate to preoperative therapy, and a sample size of 50 patients will characterize this response rate +/- 13% with 95% confidence. Secondary endpoints will include the toxicity of therapy, including surgical morbidity and mortality, the overall and disease-free survival, pattern of disease recurrence, and quality of life achieved during therapy, including relief of dysphagia. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Admin Hold | 1 |
| Overall Study | Adverse Event | 3 |
| Overall Study | Metastatic Disease | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Combined Modality Therapy for Esophageal Carcinoma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Region of Enrollment United States | 55 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 55 |
| serious Total, serious adverse events | 22 / 55 |
Outcome results
Primary
Pathologic Complete Response
Pathological information will be available for all patients who receive surgery. If a patient is deemed unresectable based on clinical and radiological examination after the therapy, that patient will be counted as non-responder. The best overall response is the best response recorded from the start of treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The subject's best response assignment will depend on the achievement of both measurement and confirmation criteria. We will also estimate the pathological complete response rates separately for each of these tumor types. Survival and disease-free survival will be estimated using Kaplan-Meier method. With an accrual rate of 3 patients a month, we expect the study to be completed in 18 months.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Modality Therapy for Esophageal Carcinoma | Pathologic Complete Response | 55 participants |
Secondary
Evaluate Toxicity and Tolerability Including Surgical Morbidity and Mortality
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Modality Therapy for Esophageal Carcinoma | Evaluate Toxicity and Tolerability Including Surgical Morbidity and Mortality | 55 participants |