Clinical trial NCT00434109: Phase II Study of Sunitinib Malate Following Hepatic Artery Embolization
Official title: Phase II Study of Sunitinib Malate Following Hepatic Artery Embolization for Metastatic Gastrointestinal Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumor
Islet Cell Tumor
Keywords: Carcinoid
Pancreatic
Metastatic
Neuroendocrine
Tumors
Hepatic
Artery
Embolization
Angiogenesis
Sunitinib
Malate
Sutent
Tyrosine
Kinase
Inhibitor
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2007-02-12
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to decide if a medicine that slows growth of new blood vessels can be give after the embolization procedure to prevent or delay new growth of blood vessels to tumors.

Detailed description: This is a single-center, open-label, non-randomized, prospective phase II trial. Sutent treatment will be continued until disease progression, or excessive toxicity (as determined by treating physician or primary investigator), or until a maximum of eight cycles, whichever duration is shorter.

Eligibility criteria: Inclusion Criteria:

* Well-differentiated metastatic carcinoid tumors and pancreatic endocrine tumors with measurable liver metastases.
* Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 grade less than or equal to 1.
* Adequate organ function as defined by the following criteria:

  1. Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) less than or equal to 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy
  2. Total serum bilirubin less than or equal to 1.5 x ULN
  3. Absolute neutrophil count (ANC) greater than or equal to 1500/microL
  4. Platelets greater than or equal to 100,000/microL
  5. Hemoglobin greater than or equal to 9.0 g/dL
  6. Serum calcium less than or equal to 12.0 mg/dL
  7. Serum creatinine less than or equal to 1.5 x ULN
  8. Prothrombin and activated partial thromboplastin time (PT and aPTT) less than or equal to 1.5 x ULN
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2
* Informed Consent: Patients must be aware of the nature of his/her disease process and must willingly give consent after being informed of the experimental nature of therapy, alternatives, potential benefits, side-effects, risks and discomforts.

Exclusion Criteria:

* Major surgery or radiation therapy within 4 weeks of starting the study treatment.
* Prior hepatic artery embolization or chemoembolization.
* Prior treatment with a tyrosine kinase inhibitor or a vascular endothelial growth factor (VEGF) inhibitor.
* NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
* History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening computed tomography (CT) or magnetic Resonance imaging (MRI) scan.
* Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
* Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2.
* Prolonged corrected QT (QTc) interval on baseline electrocardiogram (EKG).
* Hypertension that cannot be controlled by medications (\>150/100 mm Hg despite optimal medical therapy).
* Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
* Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
* Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. Quality of Life (QOL), are allowed.
* Concomitant use of ketoconazole and other agents known to induce CYP3A4.
* Concomitant use of theophylline and phenobarbital and/or other agents metabolized by the cytochrome P450 system.
* Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg by mouth (po) daily for thrombo prophylaxis is allowed).
* Pregnancy or breastfeeding. Female participants must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. Female participants with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male participants must be surgically sterile or must agree to use effective contraception during the period of therapy.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Primary outcomes:
measure: Percentage of Participants With Progression Free Survival (PFS) at 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of Participants With Overall Survival (OS) at One Year
timeFrame: 12 months
measure: Number of Participants With Partial Radiographic Response
timeFrame: 12 months
measure: Number of Participants With Biochemical Response
timeFrame: 12 months
measure: Number of Participants Requiring Dose Reduction
timeFrame: 12 months
measure: Percentage of Participants With Overall Survival (OS) at 4 Years
timeFrame: 48 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Jonathan Strosberg, MD
role: PRINCIPAL_INVESTIGATOR
References: