Combination Chemotherapy and Bevacizumab in Treating Patients With Advanced Neuroendocrine Tumors

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