Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery

This phase I/II trial studies the side effects and best dose of temozolomide and pazopanib hydrochloride when given together and to see how well they work in treating patients with advanced pancreatic neuroendocrine tumors (PNET) that cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth. Giving temozolomide together with pazopanib hydrochloride may be an effective treatment for patients with PNET.

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of temozolomide and pazopanib (pazopanib hydrochloride) combination in patients with advanced PNET. (Phase I) II. Determine the overall response rate (ORR). (Phase II)

SECONDARY OBJECTIVES:

I. Determine safety and toxicity profile of the combination of temozolomide and pazopanib in this population. (Phase I) II. Describe the pharmacokinetics of temozolomide alone and in combination with pazopanib. (Phase I) III. Observe the ORR. (Phase I) IV. Determine progression-free survival (PFS) and overall survival (OS), disease control rate (DCR), and duration of response (DOR). (Phase II) V. Determine the safety and toxicity profile of the combination in a larger cohort of patients. (Phase II)

TERTIARY OBJECTIVES:

I. Examine the relationship between tumor blood flow, as measured by perfusion functional computed tomography (f CT), and overall response.

II. Correlate the expression of tissue methyl-guanine methyl transferase (MGMT) as measured by immunohistochemistry (IHC) with ORR and PFS.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 and 15-21 and pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Eligibility Criteria:
Inclusion Criteria:

* Patients must have histologically confirmed islet cell carcinoma (PNET) not amenable to surgical resection
* Patients may have had 0-2 prior therapies; prior chemoembolization or local ablative therapies are permitted if completed \>= 6 weeks prior to study enrollment
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Patients must have a life expectancy \> 3 months
* Patients must have radiographically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
* Patients' baseline blood pressure must be adequately controlled with or without antihypertensive medications prior to enrollment (systolic \< 140 mmHg, diastolic \< 90 mmHg)
* Patients must have left ventricular ejection fraction (LVEF) \>= 50 as measured by echocardiogram or multi gated acquisition scan (MUGA)
* Absolute neutrophil count (ANC) \>= 1,500/µL
* Platelets \>= 100,000/µL
* Hemoglobin \>= 9.0 g/dL
* Total bilirubin =\< 2 mg/dL or =\< 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 5 times ULN
* International normalized ratio (INR) =\< 1.2 times upper limit of normal (ULN); subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
* Activated partial thromboplastin time (aPTT) =\< 1.2 x ULN
* Albumin \>= 2.8 g/dL
* Serum creatinine =\< 1.5 times ULN OR if serum creatinine \>= 1.5 mg/dL, calculated creatinine clearance \>= 30 mL/min
* Urine protein to creatinine ratio \< 1 OR 24-hour urine protein \< 1 g
* Patients must be able to tolerate oral medications
* Females of child-bearing potential must have a negative pregnancy test within 14 days of study enrollment and must agree to use an effective method of birth control during treatment and for three months after receiving their last dose of study drug; males must agree to use an effective method of birth control during treatment and for three months after receiving their last dose of study drug; all patients must notify treating provider immediately if any suspicion of pregnancy or conception;
* Child-bearing potential is defined as any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has NOT undergone a hysterectomy or bilateral oophorectomy; OR has NOT been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* The eligibility of patients receiving any medications or substances known or with potential to affect the activity or pharmacokinetics of temozolomide and/or pazopanib will be determined following review of the case by the Principal Investigator and the Data Monitoring Committee (DMC); efforts should be made to switch patients who are taking enzyme-inducing agents to other medications
* Patients must have given signed, informed consent prior to registration on study

Exclusion Criteria:

* Patients taking immunosuppressive medications (including systemic corticosteroids unless used for adrenal replacement), appetite stimulants, acute therapy for asthma or acute bronchitis exacerbation, or antiemetics are NOT eligible for participation
* Patients with known human immunodeficiency virus (HIV) infection are NOT eligible for participation
* Patients with uncontrolled hypertension (\>= 140/90 mmHg) are NOT eligible for participation
* Patients with uncontrolled hyperlipidemia (total cholesterol \> 350 or triglycerides \> 300) are NOT eligible for participation
* Patients who have had a transfusion within 7 days of screening are NOT eligible for participation
* Patients with symptomatic brain or bone metastasis (mets) are NOT eligible for participation; prior radiation and/or steroid therapy for brain or bone mets must be completed \>= 2 weeks prior to study enrollment
* Patients with a history of seizure disorder requiring antiepileptic medication or brain metastases with seizures are NOT eligible for participation
* Patients with an active second malignancy (other than non-melanoma skin cancer or cervical carcinoma in situ) are NOT eligible for participation; patients who have a history of malignancy are not considered to have a currently active malignancy if they have completed therapy and are now considered by their physician to be at \< 30% risk for relapse
* Patients with clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding are NOT eligible for participation; these may include (but are not limited to):
* Active peptic ulcer disease
* Known intraluminal metastatic lesion/s with risk of bleeding
* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease)
* Other gastrointestinal conditions with increased risk of perforation
* Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment are NOT eligible for participation
* Patients with clinically significant gastrointestinal abnormalities that may affect absorption of the investigational product including are NOT eligible for participation; these may include (but are not limited to):
* Malabsorption syndrome
* Major resection of the stomach or small bowel
* Patients with a history of any one or more of the following cardiovascular conditions within the past 6 months prior to study enrollment are NOT eligible for participation:
* Cardiac angioplasty or stenting
* Myocardial infarction
* Unstable angina
* Coronary artery bypass graft surgery
* Symptomatic peripheral vascular disease
* Class III or IV congestive heart failure, as defined by the New York Heart Association
* Patients with a corrected QT interval (QTc) \> 480 msecs are NOT eligible for participation
* Patients with a history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) within the past 6 months prior to study enrollment are NOT eligible for participation
* Patients with a history of any one or more of the following thromboembolic events within the past 6 months prior to study enrollment are NOT eligible for participation:
* Pulmonary embolism
* Untreated deep venous thrombosis (DVT); subjects with recent DVT who have been therapeutically coagulated for at least 6 weeks ARE eligible
* Patients who have undergone major surgery or trauma within 28 days prior to the first dose of investigational product and/or present with any non-healing wound, fracture, or ulcer are NOT eligible for participation; procedures such as catheter placement not considered to be major surgery
* Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage are NOT eligible for participation
* Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating, the vessels is acceptable; CT with contrast is strongly recommended to evaluate such lesions
* Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed
* Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
* Patients who have had recent hemoptysis (\>= 1/2 teaspoon of red blood within 8 weeks before first dose of study drug) are NOT eligible for participation
* Patients who have any history of allergic reaction(s) attributed to compounds of similar composition to temozolomide, pazopanib, their metabolites, or any component of their formulation are NOT eligible for participation
* Females who are pregnant or lactating, fertile males, or females of child-bearing potential who are not willing to comply with an effective double method of birth control are NOT eligible for participation
* Patients with a psychiatric illness, other condition or significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements are NOT eligible for participation
* Patients who have taken medications that are known strong inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) within 28 days prior to registration are NOT eligible for participation