Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Intervention: bevacizumab; cisplatin; irinotecan hydrochloride; proteomic profiling; diagnostic laboratory biomarker analysis; mass spectrometry; adjuvant therapy; neoadjuvant therapy; therapeutic conventional surgery; radiation therapy
Intervention MeSH terms: Bevacizumab; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the esophagus; recurrent esophageal cancer; stage III esophageal cancer; stage II esophageal cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others
      interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the
      growth of esophageal cancer by blocking blood flow to the tumor. Radiation therapy uses
      high-energy x-rays to kill tumor cells. Giving chemotherapy and monoclonal antibody therapy
      together with radiation therapy before surgery may make the tumor smaller and reduce the
      amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill
      any tumor cells that remain after surgery.

      PURPOSE: This phase II trial is studying how well giving irinotecan, cisplatin, and
      bevacizumab together with radiation therapy followed by surgery and bevacizumab works in
      treating patients with locally advanced esophageal cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction

               -  T1, N1, M0 or T2-4, any N, M0 esophageal carcinoma that is surgically resectable

               -  Disease must be clinically limited to the esophagus or gastroesophageal junction

                    -  If tumor extends below the gastroesophageal junction into the proximal
                       stomach, 50% of the tumor must involve the distal esophagus or
                       gastroesophageal junction

          -  No carcinoma in situ (Tis) or tumors determined to be T1, N0 after endoscopy,
             endoscopic ultrasound, or CT scan

          -  No gastric cancers with minor involvement of the gastroesophageal junction or distal
             esophagus

          -  No metastatic disease, including any of the following:

               -  M1a celiac or supraclavicular disease

               -  Positive malignant cytology of the pleura, pericardium, or peritoneum

               -  Radiographic evidence of distant organ involvement, including lung, liver, bone,
                  or brain

               -  No involvement of nonregional lymph nodes including supraclavicular or celiac
                  lymph node metastases that cannot be contained within a radiation field

          -  No biopsy-proven tumor invasion of the tracheobronchial tree or presence of
             tracheoesophageal fistula

          -  No recurrent laryngeal nerve or phrenic nerve paralysis

          -  No CNS or brain metastases

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  WBC ≥ 3,000/mm³

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9.0 g/dL

          -  INR ≤ 1.5 (except for patients requiring full-dose warfarin while on bevacizumab)

          -  Creatinine ≤ 1.5 mg/dL

          -  Bilirubin ≤ 1.5 mg/dL

          -  AST and ALT < 2.5 times normal

          -  Urine protein ≤ 1+ by urinalysis OR < 1 g of protein by 24-hour urine collection

          -  Calcium < 12 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No other prior malignancy (except for basal cell or squamous cell carcinoma of the
             skin, in situ cervical carcinoma, or superficial transitional cell bladder carcinoma)
             diagnosed and/or treated within the past 3 years

          -  No known Gilbert's disease

          -  No clinically significant hearing loss

          -  No known hypersensitivity to bevacizumab or other study drugs

          -  No severe comorbid conditions, including any of the following:

               -  Severe uncontrolled diabetes

               -  Prior stroke or cerebrovascular disease

               -  Uncontrolled infection

               -  Nonmalignant illness that precludes study treatment

          -  No history of serious systemic disease, including any of the following:

               -  Myocardial infarction within the past 6 months

               -  Uncontrolled hypertension (i.e., blood pressure > 160/110 mm Hg on medication)

               -  Unstable angina

               -  New York Heart Association class II-IV congestive heart failure

               -  Unstable symptomatic arrhythmia requiring medication

                    -  Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal
                       supraventricular tachycardia) allowed

               -  Peripheral vascular disease ≥ grade 2

          -  No significant traumatic injury within the past 28 days

          -  No evidence of bleeding diathesis or coagulopathy

          -  No other concurrent medical or psychiatric condition or disease that would preclude
             study participation

        PRIOR CONCURRENT THERAPY:

          -  No prior radiotherapy

          -  Recovered from prior oncologic or other major surgery

          -  No major surgery or open biopsy within the past 28 days

          -  No fine-needle aspiration or core biopsies within the past 7 days

          -  At least 1 week since prior and no concurrent participation in another experimental
             drug study (unless Genentech sponsored)

          -  No other concurrent major surgery

          -  No other concurrent chemotherapy

          -  No concurrent sargramostim (GM-CSF)

          -  No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital,
             Hypericum perforatum (St. John's wort), or other antiepileptic medication