| Inclusion Criteria: | 1) 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 MEN1 syndrome will be eligible and entered in the islet cell cohort
2) 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.
3) 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 VEGF or VEGF receptors (ie, SU11248, PTK787/ZK222584, Sorafinib, GW786034).
4) Patients must be on a stable dose (the same dose) of a somatostatin analogue (Lanreotide, Octreotide or Vapreotide) for 2 months prior to start of protocol. A somatostatin analogue does not count toward prior therapy.
5) Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment.
6) Patients may have received prior interferon (not counted toward prior cytotoxic chemotherapy).
7) Patients may have received prior therapy targeting c-kit, abl, PDGFR, or EGFR (imatinib, gefitanib, erlotinib, cetuximab; not counted toward prior cytotoxic chemotherapy).
8) Age >/= 21 years. GW786034 (pazopanib) is contraindicated in the pediatric population due to the potential effect on the epiphyseal growth plates.
9) Patients must have unresectable or metastatic disease.
10) ECOG performance status of 0, or 1 (Karnofsky >/= 70%).
11) Patients must have normal organ and marrow function as defined below: Leukocytes >/= 3,000/mcL; absolute neutrophil count >/= 1,500/mcL; platelets >/= 120,000/mcL; total bilirubin within normal institutional limits; AST(SGOT)/ALT(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)
12) Patients must have PT/INR/PTT within 1.2 X the upper limit of normal.
13) 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.
14) The effects of GW786034 (pazopanib) on the developing human fetus are unknown. However, teratogenic effects and reduced fetal body weight have been seen in pregnant rats and/or rabbits given GW786034 (pazopanib). For this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
15) 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.
16) 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;
17) Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows; 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). Oral contraceptives are not reliable due to potential drug-drug interaction.
18) Ability to understand and the willingness to sign a written informed consent document.
19) Ability to swallow and retain oral medication
20) Both men and women and members of all races and ethnic groups are eligible for this trial. |