Combination Chemotherapy and Bevacizumab in Treating Patients With Advanced Neuroendocrine Tumors

You may be eligible if

• DISEASE CHARACTERISTICS:
• Histologically or cytologically confirmed neuroendocrine tumor (NET)
• * Carcinoid at any site, with or without carcinoid syndrome
• * Pancreatic islet cell tumor
• * Prior streptozocin-based therapy not required
• * Poorly differentiated NET of any primary site (this arm closed to accrual May 2009)
• * Progression with prior treatment with cisplatin-, or carboplatin-based chemotherapy required (unless contraindicated)
• The following tumors are not allowed:
• * Endocrine organ carcinoma
• * Adrenal gland malignancies
• * Thyroid carcinoma of any histology
• * Pheochromocytoma/paraganglioma
• Advanced disease
• * Disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent
• Radiologically or clinically confirmed progressive disease
• * At least 25% increase in radiologically or clinically measurable disease
• * At least 20% increase in the longest diameter (LD) of any previously documented lesion
• * Increase in the sum of the LD of multiple lesions in aggregate of 20%, OR appearance of new lesions OR deterioration in clinical status
• Measurable disease
• * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional radiographic techniques OR ≥ 10 mm by spiral CT scan
• * Ultrasound or positron-emission tomography alone not sufficient
• * Bone lesions, ascites, peritoneal carcinomatosis, pleural or pericardial effusion, and irradiated lesions are not considered measurable disease
• Primary tumors of the pancreas should not invade adjacent organs (e.g., stomach or duodenum)
• No history or evidence of brain or leptomeningeal disease (baseline CNS imaging required if clinical suspicion of CNS metastases)
• PATIENT CHARACTERISTICS:
• Age
• 18 and over
• Performance status
• ECOG 0-1
• Life expectancy
• More than 12 weeks
• Hematopoietic
• Absolute neutrophil count ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• No history of hemoptysis or bleeding diathesis
• No coagulopathy unrelated to therapeutic anticoagulation
• No significant bleeding events within the past 6 months unless the source of the bleeding has been resected
• Hepatic
• Bilirubin \< 2 mg/dL
• ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastases)
• Renal
• Creatinine ≤ 2 mg/dL
• Protein ≤ 1+ OR
• Protein \< 1 gm on 24-hour urine collection
• Urine protein:creatinine ratio \< 1.0
• Cardiovascular
• History of thromboembolic condition allowed provided patient is on therapeutic anticoagulation at a stable dose for ≥ 4 weeks
• * Concurrent daily prophylactic aspirin (\< 325 mg/day) allowed
• No uncontrolled hypertension, myocardial infarction, clinically significant peripheral arterial ischemia, visceral arterial ischemia or angina within the past 6 months
• No serious cardiac arrhythmia requiring medication
• No cerebrovascular event (e.g., stroke or transient ischemic attack) within the past 12 months
• No history of peripheral vascular disease ≥ grade 2
• No history New York Heart Association class II-IV congestive heart failure
• Blood pressure ≤ 160/90 mm Hg
• Gastrointestinal
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No predisposing uncontrolled small bowel or colonic disorder
• * Baseline disease-related diarrhea allowed if symptoms are stable and well-characterized (i.e., # stools/day stable)
• No gastric or esophageal varices
• No gastroduodenal ulcers determined to be active by endoscopy
• Pulmonary
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis
• No lung tumor in close proximity to a major vessel, or with associated cavitation
• No pleural effusion or ascites that causes ≥ grade 2 dyspnea
• Other
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment
• No significant traumatic injury within the past 28 days
• No currently active second malignancy other than, non-melanoma skin cancer or carcinoma in situ
• * Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at ≤ 30% risk for relapse
• No known hypersensitivity reaction attributed to study drugs or to compounds of similar chemical or biological composition
• No symptomatic peripheral neuropathy \> grade 1
• No other severe disease or comorbidity that would preclude study participation
• No medically uncontrolled seizures
• No active infection
• No serious non-healing wound, ulcer, or bone fracture
• No psychiatric illness or social situation that would preclude study compliance
• No other severe, concurrent disease, infection, or co-morbidity that in the judgement of the investigator would constitute a hazard for study participation
• PRIOR CONCURRENT THERAPY:
• Biologic therapy
• Recovered from prior cytokine therapy
• At least 4 weeks since prior immunotherapy
• No prior tyrosine kinase inhibitors or anti-vascular endothelial growth factor (VEGF) angiogenic inhibitors
• Chemotherapy
• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No prior oxaliplatin
• Prior chemoembolization therapy allowed provided it did not affect areas of measurable disease
• Endocrine therapy
• Prior and concurrent somatostatin analogs allowed for symptomatic control and/or control of hormone hypersecretion only provided treatment was initiated \> 3 months prior to study entry
• Radiotherapy
• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• * Prior radiotherapy must not affect areas of measurable disease
• No concurrent radiotherapy to only site of measurable disease
• Surgery
• Recovered from prior surgery
• Prior cryotherapy allowed provided it did not affect areas of measurable disease
• At least 28 days since prior major surgical procedure or open biopsy
• At least 7 days since minor surgical procedure, fine-needle aspirations, or core biopsy
• No prior organ allograft
• No concurrent major surgery
• Other
• At least 4 weeks since prior participation in an experimental drug study
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No halogenated antiviral agents
• Concurrent antiplatelet agents allowed