Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

NCT00454363 | Completed Phase 2 Results

• 7 other identifiers: NCI-2009-00201CDR0000537034MDACC 2006-00777650N01CM62202P30CA016672U01CA062490
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 18 months

Secondary Outcomes (1)

• Percent Change in Tumor Blood Flow Assessed by Functional CT

  Baseline and week 12

Other Outcomes (2)

• Progression Free Survival (PFS)

  Baseline to 18 months.

• Plasma Trough Level of GW786034

  assessed at Baseline and day 28, day 28 reported

Study Arms (1)

Treatment (pazopanib hydrochloride)

EXPERIMENTAL

Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pazopanib hydrochloride)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Treatment (pazopanib hydrochloride)

Pharmacological Study OTHER

Correlative studies

Treatment (pazopanib hydrochloride)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Phan AT, Halperin DM, Chan JA, Fogelman DR, Hess KR, Malinowski P, Regan E, Ng CS, Yao JC, Kulke MH. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study. Lancet Oncol. 2015 Jun;16(6):695-703. doi: 10.1016/S1470-2045(15)70136-1. Epub 2015 May 5.

  PMID: 25956795 DERIVED

MeSH Terms

Conditions

Zollinger-Ellison Syndrome; Multiple Endocrine Neoplasia Type 1; Glucagonoma; Insulinoma; Somatostatinoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Carcinoma, Islet Cell; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pancreatic Neoplasms; Pancreatic Diseases; Adenoma, Islet Cell; Adenoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal

Results Point of Contact

• Title: Dr. James Yao, MD/Professor, GI Medical Oncology, Study Principal Investigator
• Organization: UT MD Anderson Cancer Center

jyao@mdanderson.org

713-792-2828

Study Officials

• James Yao

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2007
• First Posted: March 30, 2007
• Study Start: March 1, 2007
• Primary Completion: March 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 3, 2020
• Results First Posted: April 1, 2015

Record last verified: 2020-03

Locations

US (3)