Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer
Condition: Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Multiple Endocrine Neoplasia Type 1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor
MeSH terms: Carcinoma; Neuroendocrine Tumors; Carcinoid Tumor; Carcinoma, Neuroendocrine; Insulinoma; Endocrine Gland Neoplasms; Multiple Endocrine Neoplasia; Glucagonoma; Intestinal Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Malignant Carcinoid Syndrome; Gastrointestinal Neoplasms; Multiple Endocrine Neoplasia Type 1; Carcinoma, Islet Cell; Somatostatinoma; Gastrinoma; Recurrence
Intervention: Laboratory Biomarker Analysis; Pazopanib Hydrochloride; Pharmacological Study
Intervention description: Correlative studies; Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pazopanib hydrochloride works in treating patients with
      advanced neuroendocrine cancer. Pazopanib hydrochloride may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed low or intermediate grade
             carcinoid or islet cell carcinoma; patients with carcinoid or islet cell carcinoma
             associated with multiple endocrine neoplasia (MEN)1 syndrome will be eligible and
             entered in the islet cell cohort

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral CT scan

          -  Patients may have received 0 or 1 prior cytotoxic therapy; chemotherapy used as a
             radiosensitizer will be considered one prior chemotherapy regimen; patient must not
             have received prior bevacizumab or any other therapy targeting vascular endothelial
             growth factor (VEGF) or VEGF receptors (i.e., SU11248, PTK787/ZK222584, Sorafenib,
             GW786034)

          -  Patients must be on a stable dose of somatostatin analogue for 2 months prior to start
             of protocol; octreotide dose not count toward prior therapy

          -  Prior radiation therapy is permitted; a recovery period of at least 4 weeks after
             completion of radiotherapy is required prior to enrollment

          -  Patients may have received prior interferon (not counted toward prior cytotoxic
             chemotherapy)

          -  Patients may have received prior therapy targeting v-kit Hardy-Zuckerman 4 feline
             sarcoma viral oncogene homolog (c-kit), c-abl oncogene 1, non-receptor tyrosine kinase
             (abl), platelet-derived growth factor receptor (PDGFR), or epidermal growth factor
             receptor (EGFR) (imatinib, gefitinib, erlotinib, cetuximab; not counted toward prior
             cytotoxic chemotherapy)

          -  Patients must have unresectable or metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1 (Karnofsky >=
             70%)

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 120,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3.0 X institutional upper limit of normal

          -  Creatinine =< 2.0 OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with
             creatinine levels above institutional normal (calculated by Cockcroft Gault formula)

          -  Patients must have prothrombin time (PT)/international normalized ratio (INR)/partial
             thromboplastin time (PTT) within 1.2 X the upper limit of normal

          -  Patients must have resting blood pressure (BP) no greater than 140 mmHg (systolic) or
             90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is
             permitted prior to study entry

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry and for the duration of study participation; women of
             child-bearing potential must have a negative blood pregnancy test prior to study
             entry; should a woman become pregnant or suspect she is pregnant while participating
             in this study, she should inform her treating physician immediately; acceptable
             contraceptive methods, when used consistently and in accordance with both the product
             label and the instructions of the physician, are as follows:

               -  An intrauterine device with a documented failure rate of less than 1% per year

               -  Vasectomized partner who is sterile prior to the female patient's entry and is
                  the sole sexual partner for that female

               -  Complete abstinence from sexual intercourse for 14 days before exposure to
                  investigation product, through the clinical trial, and for at least 21 days after
                  the last dose of investigational product

               -  Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
                  film; diaphragm with spermicide; or male condom and diaphragm with spermicide)

                    -  Note: Oral contraceptives are not reliable due to potential drug-drug
                       interaction

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Ability to swallow and retain oral medication

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks prior to study
             enrollment; at least 4 weeks must have elapsed since any major surgery prior to study
             enrollment

          -  Patients may not be receiving any other investigational agents

          -  Patients with corrected QT (QTc) > 480 msecs

          -  Patients with greater than 1+ (>= 100 mg/dl) proteinuria on two consecutive routine
             urinalysis taken at least 1 week apart are ineligible

          -  Certain medications that act through the cytochrome P450 (CYP450) system are
             specifically prohibited in patients receiving GW786034 (pazopanib) because in vitro
             data indicate that the agent has the potential to interact with the cytochrome P450
             isoenzymes; certain other agents should be used with caution

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for intravenous [IV] alimentation,
             prior surgical procedures affecting absorption, or active peptic ulcer disease) that
             impairs their ability to swallow and retain GW786034 (pazopanib) tablets are excluded

          -  Patients with any of the following conditions are excluded:

               -  Serious or non-healing wound, ulcer, or bone fracture

               -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
                  abscess within 28 days of treatment

               -  History of known active diverticulitis within the past 3 months

               -  Any history of cerebrovascular accident (CVA) within the last 6 months

               -  Current use of therapeutic warfarin; Note: Low molecular weight heparin and
                  prophylactic low-dose warfarin are permitted; PT/PTT must meet the inclusion
                  criteria

               -  History of myocardial infarction, cardiac arrhythmia, admission for unstable
                  angina, cardiac angioplasty or stenting within the last 12 weeks

               -  History of venous thrombosis in last 12 weeks

               -  Class III or IV heart failure as defined by the New York Heart Association (NYHA)
                  functional classification system; a patient who has a history of class II heart
                  failure and is asymptomatic on treatment may be considered eligible

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, or other adequately treated in situ cancer,
             or any other cancer from which the patient has been disease free for five years

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with GW786034 (pazopanib); these potential risks may also apply
             to other agents used in this study

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Uncontrolled diarrhea (8 or more bowel movements per day)