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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 pancreatic neuroendocrine tumors (PNET) that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) and 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, by stopping them from dividing, or by stopping them from spreading. 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 a better treatment for patients with PNET.
Not Available
Phase I/II
Adults
Not Available
Not Available
Not Available
National
Vanderbilt University
04-09-2013
Treatment
VICCGI1250
NCT01465659

Eligibility

18 Years
BOTH
NO
Inclusion Criteria:

Patients must have histologically confirmed well-differentiated islet cell carcinoma (PNET) not amenable to surgical resection

Patients may have had 0-4 prior therapies * Prior chemoembolization or local ablative therapies are permitted if completed >= 6 weeks prior to study enrollment * Prior temozolomide is permitted

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =
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
Patients must have left ventricular ejection fraction (LVEF) >= 50 as measured by echocardiogram or multigated acquisition scan (MUGA)

Absolute neutrophil count (ANC) >= 1,500/uL

Platelets >= 100,000/uL

Hemoglobin >= 9.0 g/dL

Total bilirubin =
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =
International normalized ratio (INR) =
Activated partial thromboplastin time (aPTT) =
Albumin >= 2.8 g/dL

Serum creatinine == 1.5 mg/dL, calculated creatinine clearance >= 30 mL/min

Urine protein to creatinine ratio
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; 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 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 are NOT eligible for participation; prior radiation and/or steroid therapy for brain or bone metastasis (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
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 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, family 3, subfamily A, polypeptide 4 (CYP3A4) within 28 days prior to registration are NOT eligible for participation

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