Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer

• Status: Completed
• Trial end date: 2015-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bevacizumab; Camptothecin; Cisplatin; Irinotecan

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