Cisplatin, Irinotecan, and Radiation Therapy in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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This phase II trial studies how well giving cisplatin and irinotecan hydrochloride together with radiation therapy works in treating patients with esophageal cancer or gastroesophageal junction cancer that can be removed by surgery. Drugs used in chemotherapy, such as cisplatin and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the pathologic complete response rate in patients with surgically resectable esophageal cancer treated pre-operatively with induction chemotherapy with weekly cisplatin and irinotecan (irinotecan hydrochloride) followed by concurrent cisplatin/irinotecan and radiation therapy. SECONDARY OBJECTIVES: I. To evaluate potential response or progression of disease during induction chemotherapy with positron emission tomography (PET) scan. II. To evaluate the toxicity and tolerability of therapy, including surgical morbidity and mortality. III. To determine the overall survival, disease free survival, and pattern of failure. OUTLINE: INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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A Phase II Trial of Preoperative Irinotecan, Cisplatin and Radiation in Esophageal Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: irinotecan hydrochloride
* Procedure: therapeutic conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Histologically or cytologically confirmed adenocarcinoma, poorly differentiated carcinoma, or carcinoma not otherwise specified, of the esophagus or gastroesophageal junction; biopsy or cytology of the primary tumor, or of involved regional lymph nodes, is acceptable Tumors must be TNM stage T2-4, N0-1, M0 as determined by pretreatment endoscopic ultrasound; T1 tumors are eligible if they are T1, N1, M0; regional thoracic lymph node involvement (N1) is permitted Disease must be clinically limited to the esophagus or gastroesophageal junction; if the tumor extends below the gastroesophageal junction into the proximal stomach, 50% of the tumor must involve the distal esophagus or gastroesophageal junction; adenocarcinomas of the distal esophagus would therefore include tumors of the distal esophagus, or Siewert type I according to the Siewert classification, and tumors of the gastroesophageal junction which involve equally both the distal esophagus and proximal stomach, or Siewert type II; tumor must be surgically resectable No TIS (in-situ carcinoma) and tumors determined to be T1N0 following endoscopic ultrasound No clinical involvement on endoscopic ultrasound (EUS), computed tomography (CT) scan, or PET scan of supraclavicular or celiac lymph node involvement (stage IVa, T any N any M1a) unless this is proven to be a false positive by an appropriate biopsy No patients with cervical esophageal tumors, or gastric cancers with minor involvement of the gastroesophageal junction or distal esophagus No patients with tracheoesophageal fistulas Patients with evidence of metastatic disease are not eligible; this includes: Positive malignant cytology of the pleura, pericardium or peritoneum Radiographic evidence of distance organ involvement including lung, liver, bone, or brain No prior chemotherapy or radiotherapy is permitted; patients must be at least 4 weeks since major surgery, or must have recovered from the effects of minor surgery (laparoscopy, thoracoscopy) No prior malignancies (other than basal cell/squamous carcinoma of the skin, in-situ cervical carcinoma, or superficial transitional cell bladder carcinoma) are permitted unless diagnosed and/or treated >= 3 years before registration and without evidence of recurrence Eastern Cooperative Oncology Group (ECOG) performance status 0-1 No evidence of recurrent laryngeal nerve or phrenic nerve paralysis No known Gilbert's disease No clinically significant hearing loss; audiograms should be done in patients in which they are clinically indicated No history of active seizure disorder; no ongoing treatment with phenytoin, phenobarbital, or other antiepileptic medication; patients who are receiving valproic acid are eligible No New York Heart Association class III or IV heart disease; no angina or myocardial infarction within the last 6 months Inclusion Criteria: No history of clinically significant ventricular arrhythmia requiring ongoing medication with antiarrhythmics Absolute neutrophil count (ANC) >= 1,500/ul Platelet count >= 100,000/ul Hemoglobin >= 9 gm/dl Serum creatinine =< upper limit of normal (ULN) Total serum bilirubin =< 1.5 mg/dl Forced expiratory volume in 1 second (FEV-1) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size Pulmonary function tests (PFT) >= 1.2 liters OR >= 35% of normal as a value that is indexed to body size

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy, chemoradiotherapy, surgery)<br>INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery to remove the tumor. | Drug: cisplatin<br>* Given IV<br>Drug: irinotecan hydrochloride<br>* Given IV<br>Procedure: therapeutic conventional surgery<br>* Undergo Surgery<br>Radiation: radiation therapy<br>* Undergo radiation<br>* Other names: irradiation, radiotherapy, therapy, radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Adenocarcinoma Achieving a Pathologic Complete Response (CR) After Surgery | A pathological complete response is defined as no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Utility of Early PET Imaging in Predicting Response to Treatment |  | Up to 55 days | 
| Disease-free Survival |  | Up to 5 years | 
| Overall Survival |  | Up to 5 years | 
| Patterns of Failure |  | Up to 5 years | 
| Proportion of Patients Experiencing Grade 3 or Greater Pneumonitis or Esophagitis | Proportion of patients experiencing grade 3 or greater pneumonitis or esophagitis, deemed at least possibly related to treatment graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 | Up to 5 years | 
| Proportion of Patients Experiencing Grade 3 or Greater Hematologic and Non-hematologic Toxicity | Proportion of patients experiencing grade 3 or greater hematologic and non-hematologic toxicity, deemed as at least possibly related to treatment, graded using the NCI CTCAE version 3.0 | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer