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
Conditions
Brief 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.
Detailed description
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) (complete and partial response) of GW786034 (pazopanib hydrochloride) 800 mg administered orally once daily in patients with advanced low or intermediate grade carcinoid tumors (in carcinoid cohort). II. To determine the objective response rate (ORR) (complete response and partial response) of GW786034 800mg administered orally once daily in patients with advanced low or intermediate grade pancreatic islet cell carcinoma (in islet cell cohort). SECONDARY OBJECTIVES: I. To determine the progression free survival (PFS) duration of GW786034 800mg administered orally once daily in patients with low grade neuroendocrine carcinoma. II. To determine the safety and tolerability of GW786034 800mg administered orally once daily in patients with low grade neuroendocrine carcinoma. III. To explore the effect on tumor blood flow as determined by functional computed tomography (CT) of GW786034 800 mg orally once daily in patients with low grade neuroendocrine carcinoma. IV. To assess the trough level of GW786034 800 mg orally once daily in patients with low grade neuroendocrine carcinoma. OUTLINE: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 90 days for up to 18 months.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPazopanib Hydrochloride
Given PO
OTHERPharmacological Study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Up to 18 months | RECIST Criteria: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance 1/\> new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Tumor Blood Flow Assessed by Functional CT | Baseline and week 12 | Explore the effect on tumor blood flow as determined by functional CT of GW786034 (Pazopanib) 800 mg orally once daily on both arms, carcinoid and pNET. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline to 18 months. | PFS is defined as the duration of time from start of treatment to time of progression or death. |
| Plasma Trough Level of GW786034 | assessed at Baseline and day 28, day 28 reported | — |
Countries
United States
Participant flow
Recruitment details
Open recruitment period: March 2007 to December 2009. All recruitment done at University of Texas (UT) and Dana Farber Cancer Institute.
Pre-assignment details
Of the 52 enrolled, one participant was excluded from the study prior to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Pazopanib + Carcinoid Carcinoid Tumor Type: Oral Pazopanib hydrochloride 800 mg once daily on days 1-28. | 20 |
| Pazopanib + pNET Pancreatic Neuroendocrine (pNET) tumor type: Oral Pazopanib hydrochloride 800 mg once daily on days 1-28. | 31 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Withdrawal prior to 12 weeks treatment | 4 | 0 |
Baseline characteristics
| Characteristic | Pazopanib + pNET | Total | Pazopanib + Carcinoid |
|---|---|---|---|
| Age, Continuous | 55 years | 60 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 46 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Participant from Enrolling Institutions Dana Farber Cancer Institute | 11 participants | 17 participants | 6 participants |
| Participant from Enrolling Institutions MD Anderson Cancer Center | 20 participants | 34 participants | 14 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 48 Participants | 20 Participants |
| Region of Enrollment United States | 31 participants | 51 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 17 Participants | 7 Participants |
| Sex: Female, Male Male | 21 Participants | 34 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 51 |
| serious Total, serious adverse events | 16 / 51 |
Outcome results
Primary
Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
RECIST Criteria: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance 1/\> new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.
Time frame: Up to 18 months
Population: RECIST best protocol response by intention to treat. Four participants were not evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pazopanib + Carcinoid | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | PR | 0 participants |
| Pazopanib + Carcinoid | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | SD | 14 participants |
| Pazopanib + Carcinoid | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | PD | 3 participants |
| Pazopanib + Carcinoid | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Not Evaluable | 3 participants |
| Pazopanib + pNET | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Not Evaluable | 1 participants |
| Pazopanib + pNET | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | PR | 6 participants |
| Pazopanib + pNET | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | PD | 3 participants |
| Pazopanib + pNET | Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | SD | 21 participants |
Secondary
Percent Change in Tumor Blood Flow Assessed by Functional CT
Explore the effect on tumor blood flow as determined by functional CT of GW786034 (Pazopanib) 800 mg orally once daily on both arms, carcinoid and pNET.
Time frame: Baseline and week 12
Population: Data were not collected from any participant in the Pazopanib + Carcinoid Arm Group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pazopanib + pNET | Percent Change in Tumor Blood Flow Assessed by Functional CT | 139 percentage of change in tumor blood flow |
Other Pre-specified
Plasma Trough Level of GW786034
Time frame: assessed at Baseline and day 28, day 28 reported
Population: Plasma trough level in blood was below the level of detection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pazopanib + Carcinoid | Plasma Trough Level of GW786034 | NA Participants |
| Pazopanib + pNET | Plasma Trough Level of GW786034 | NA Participants |
Other Pre-specified
Progression Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death.
Time frame: Baseline to 18 months.
Population: Analysis calculated according to intent to treat.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pazopanib + Carcinoid | Progression Free Survival (PFS) | 12 months |
| Pazopanib + pNET | Progression Free Survival (PFS) | 14.2 months |